Publications by authors named "Abbas Shafiee"

284 Publications

Correction: Humanized bone facilitates prostate cancer metastasis and recapitulates therapeutic effects of Zoledronic acid in vivo.

Bone Res 2020 Apr 3;8(1):17. Epub 2020 Apr 3.

Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.

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http://dx.doi.org/10.1038/s41413-020-0092-5DOI Listing
April 2020

Mechanical environment for lower canine T-loop retraction compared to en-masse space closure with a power-arm attached to either the canine bracket or the archwire.

Angle Orthod 2020 11;90(6):801-810

Objectives: To assess the mechanical environment for three fixed appliances designed to retract the lower anterior segment.

Materials And Methods: A cone-beam computed tomography scan provided three-dimensional morphology to construct finite element models for three common methods of lower anterior retraction into first premolar extraction spaces: (1) canine retraction with a T-loop, (2) en-masse space closure with the power-arm on the canine bracket (PAB), and (3) power-arm directly attached to the archwire mesial to the canine (PAW). Half of the symmetric mandibular arch was modeled as a linear, isotropic composite material containing five teeth: central incisors (L1), lateral incisor (L2), canine (L3), second premolar (L4), and first molar (L5). Bonded brackets had 0.022-in slots. Archwire and power-arm components were 0.016 × 0.022 in. An initial retraction force of 125 cN was used for all three appliances. Displacements were calculated. Periodontal ligament (PDL) stresses and distributions were calculated for four invariants: maximum principal, minimum principal, von Mises, and dilatational stresses.

Results: The PDL stress distributions for the four invariants corresponded to the displacement patterns for each appliance. T-loop tipped the canine(s) and incisors distally. PAB rotated L3 distal in, intruded L2, and extruded L1. PAW distorted the archwire resulting in L3 extrusion as well as lingual tipping of L1 and L2. Maximum stress levels in the PDL were up to 5× greater for the PAW than the T-loop and PAB methods.

Conclusions: T-loop of this type is more predictable because power-arms can have rotational and archwire distortion effects that result in undesirable paths of tooth movement.
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http://dx.doi.org/10.2319/050120-377.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028426PMC
November 2020

Convergence of 3D printed biomimetic wound dressings and adult stem cell therapy.

Biomaterials 2021 Jan 27;268:120558. Epub 2020 Nov 27.

Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Brisbane, QLD, 4059, Australia; Australian Research Council (ARC) Training Centre in Additive Biomanufacturing, Queensland University of Technology (QUT), Kelvin Grove, QLD, 4059, Australia. Electronic address:

Biomimetically designed medical-grade polycaprolactone (mPCL) dressings are 3D-printed with pore architecture and anisotropic mechanical characteristics that favor skin wound healing with reduced scarring. Melt electrowritten mPCL dressings are seeded with human gingival tissue multipotent mesenchymal stem/stromal cells and cryopreserved using a clinically approved method. The regenerative potential of fresh or frozen cell-seeded mPCL dressing is compared in a splinted full-thickness excisional wound in a rat model over six weeks. The application of 3D-printed mPCL dressings decreased wound contracture and significantly improved skin regeneration through granulation and re-epithelialization compared to control groups. Combining 3D-printed biomimetic wound dressings and precursor cell delivery enhances physiological wound closure with reduced scar tissue formation.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120558DOI Listing
January 2021

Synergistic therapeutic effect of mesenchymal stem cells and tolerogenic dendritic cells in an acute colitis mouse model.

Int Immunopharmacol 2020 Nov 23;88:107006. Epub 2020 Sep 23.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Cell-based therapy with tolerizing cells has been applied for the treatment of inflammatory bowel disease (IBD) in previous experimental and clinical studies with promising results. In the current study, we utilized the dextran sulfate sodium (DSS)-induced colitis model, to investigate if tolerogenic dendritic cell-mesenchymal stem cell (tDC-MSC) combination therapy can augment the therapeutic effects of single transplantation of each cell type. The effect of MSC and tDC co-transplantation on the severity of colitis was assessed by daily monitoring of body weight, stool consistency, and rectal bleeding, and compared with control groups. Moreover, the colon length, colon weight, myeloperoxidase (MPO) activity were measured and evaluated with histological analysis of colon tissues. The Treg cell percentage and cytokine levels in spleens and mesenteric lymph nodes (MLNs) were measured by flow cytometry and ELISA, respectively. The results showed co-transplantation of MSCs and tDCs was more effective in alleviating the clinical and histological manifestations of colitis than monotherapy, especially when compared with MSC alone. The protective effects of tDC-MSC were accompanied by the induction of Treg cells and increased the production of anti-inflammatory cytokines in spleens and mesenteric lymph nodes. Together, co-transplantation of MSCs and tDCs could be a promising and effective therapeutic approach in the treatment of IBD.
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http://dx.doi.org/10.1016/j.intimp.2020.107006DOI Listing
November 2020

A 3D-printed biomaterials-based platform to advance established therapy avenues against primary bone cancers.

Acta Biomater 2020 12 8;118:69-82. Epub 2020 Oct 8.

Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, QLD 4059, Brisbane, Australia; ARC Training Centre in Additive Biomanufacturing, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia; School of Mechanical, Medical and Process Engineering, Queensland University of Technology (QUT), 2 George Street, Brisbane, QLD 4001, Australia. Electronic address:

In this study we developed and validated a 3D-printed drug delivery system (3DPDDS) to 1) improve local treatment efficacy of commonly applied chemotherapeutic agents in bone cancers to ultimately decrease their systemic side effects and 2) explore its concomitant diagnostic potential. Thus, we locally applied 3D-printed medical-grade polycaprolactone (mPCL) scaffolds loaded with Doxorubicin (DOX) and measured its effect in a humanized primary bone cancer model. A bioengineered species-sensitive orthotopic humanized bone niche was established at the femur of NOD-SCID IL2Rγ (NSG) mice. After 6 weeks of in vivo maturation into a humanized ossicle, Luc-SAOS-2 cells were injected orthotopically to induce local growth of osteosarcoma (OS). After 16 weeks of OS development, a biopsy-like defect was created within the tumor tissue to locally implant the 3DPDDS with 3 different DOX loading doses into the defect zone. Histo- and morphological analysis demonstrated a typical invasive OS growth pattern inside a functionally intact humanized ossicle as well as metastatic spread to the murine lung parenchyma. Analysis of the 3DPDDS revealed the implants' ability to inhibit tumor infiltration and showed local tumor cell death adjacent to the scaffolds without any systemic side effects. Together these results indicate a therapeutic and diagnostic capacity of 3DPDDS in an orthotopic humanized OS tumor model.
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http://dx.doi.org/10.1016/j.actbio.2020.10.006DOI Listing
December 2020

Mesenchymal stem cell therapies for COVID-19: Current status and mechanism of action.

Life Sci 2020 Dec 23;262:118493. Epub 2020 Sep 23.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

The outbreak of COVID-19 in December 2019, has become an urgent and serious public health emergency. At present, there is no effective treatment or vaccine for COVID-19. Therefore, there is a crucial unmet need to develop a safe and effective treatment for COVID-19 patients. Mesenchymal stem cells (MSCs) are widely used in basic science and in a variety of clinical trials. MSCs are able to engraft to the damaged tissues after transplantation and promote tissue regeneration, besides MSCs able to secrete immunomodulatory factors that suppress the cytokine storms. Moreover, the contribution of MSCs to prevent cell death and inhibit tissue fibrosis is well established. In the current review article, the potential mechanisms by which MSCs contribute to the treatment of COVID-19 patients are highlighted. Also, current trials that evaluated the potential of MSC-based treatments for COVID-19 are briefly reviewed.
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http://dx.doi.org/10.1016/j.lfs.2020.118493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510562PMC
December 2020

Immunomodulatory and Therapeutic Effects of Mesenchymal Stem Cells on Organ Dysfunction in Sepsis.

Shock 2021 Apr;55(4):423-440

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract: Sepsis is a life-threatening disorder that is caused by a dysregulated inflammatory response during an infection. The disease mostly affects pregnant women, newborns, and patients in intensive care units. Sepsis treatment is a significant part of a country's health budgets. Delay in the therapy causes irreversible failure of various organs due to the lack of blood supply and reduction of oxygen in the tissues and eventually increased mortality. The involvement of four or five organs by sepsis has been attributed to an increased risk of death to over 90%. Although antibiotics are at the first line of sepsis treatment, they do not possess enough potency to control the disease and prevent subsequent organ failure. The immunomodulatory, anti-inflammatory, anti-apoptotic, and anti-microbial properties of mesenchymal stem cells (MSCs) have been reported in various studies. Therefore, the application of MSCs has been considered a potentially promising therapeutic strategy. In preclinical studies, the administration of MSCs has been associated with reduced bacterial load and decreased levels of pro-inflammatory factors as well as the improved function of the different vital organs, including heart, kidney, liver, and lungs. The current study provides a brief review of sepsis and its pathophysiology, and then highlights recent findings in the therapeutic effects of MSCs and MSC-derived secretome in improving sepsis-induced organ dysfunction. Besides, eligible sepsis candidates for MSC-therapy and the latest clinical findings in these areas have been reviewed.
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http://dx.doi.org/10.1097/SHK.0000000000001644DOI Listing
April 2021

Coronavirus disease 2019: A tissue engineering and regenerative medicine perspective.

Stem Cells Transl Med 2021 01 21;10(1):27-38. Epub 2020 Aug 21.

Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, Queensland, Australia.

Current therapies for novel coronavirus disease (COVID-19) are generally used to manage rather than cure this highly infective disease. Therefore, there is a significant unmet medical need for a safe and effective treatment for COVID-19. Inflammation is the driving force behind coronavirus infections, and the majority of deaths caused by COVID-19 are the result of acute respiratory distress syndrome (ARDS). It is crucial to control the inflammation as early as possible. To date, numerous studies have been conducted to evaluate the safety and efficacy of tissue engineering and regenerative medicine (TERM) products, including mesenchymal stem cells (MSCs), and their derivatives (eg, exosomes) for coronavirus infections, which could be applied for the COVID-19. In this review, first, the impacts of the COVID-19 pandemic in the present and future of TERM research and products are briefly presented. Then, the recent clinical trials and the therapeutic benefits of MSCs in coronavirus-induced ARDS are critically reviewed. Last, recent advances in the field of tissue engineering relevant to coronavirus infections, including three-dimensional platforms to study the disease progression and test the effects of antiviral agents, are described. Moreover, the application of biomaterials for vaccine technology and drug delivery are highlighted. Despite promising results in the preclinical and clinical applications of MSC therapy for coronavirus infections, controversy still exists, and thus further investigation is required to understand the efficacy of these therapies.
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http://dx.doi.org/10.1002/sctm.20-0197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461291PMC
January 2021

Engineering a Humanised Niche to Support Human Haematopoiesis in Mice: Novel Opportunities in Modelling Cancer.

Cancers (Basel) 2020 Aug 6;12(8). Epub 2020 Aug 6.

Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Queensland 4059, Australia.

Despite the bone marrow microenvironment being widely recognised as a key player in cancer research, the current animal models that represent a human haematopoietic system lack the contribution of the humanised marrow microenvironment. Here we describe a murine model that relies on the combination of an orthotopic humanised tissue-engineered bone construct (ohTEBC) with patient-specific bone marrow (BM) cells to create a humanised bone marrow (hBM) niche capable of supporting the engraftment of human haematopoietic cells. Results showed that this model supports the engraftment of human CD34 cells from a healthy BM with human haematopoietic cells migrating into the mouse BM, human BM compartment, spleen and peripheral blood. We compared these results with the engraftment capacity of human CD34 cells obtained from patients with multiple myeloma (MM). We demonstrated that CD34 cells derived from a diseased BM had a reduced engraftment potential compared to healthy patients and that a higher cell dose is required to achieve engraftment of human haematopoietic cells in peripheral blood. Finally, we observed that hematopoietic cells obtained from the mobilised peripheral blood of patients yields a higher number of CD34, overcoming this problem. In conclusion, this humanised mouse model has potential as a unique and patient-specific pre-clinical platform for the study of tumour-microenvironment interactions, including human bone and haematopoietic cells, and could, in the future, serve as a drug testing platform.
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http://dx.doi.org/10.3390/cancers12082205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466161PMC
August 2020

Correction: Humanized bone facilitates prostate cancer metastasis and recapitulates therapeutic effects of Zoledronic acid in vivo.

Bone Res 2020;8:17. Epub 2020 Apr 3.

1Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.

[This corrects the article DOI: 10.1038/s41413-019-0072-9.].
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http://dx.doi.org/10.1038/s41413-020-0092-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118404PMC
April 2020

Targeted camptothecin delivery via silicon nanoparticles reduces breast cancer metastasis.

Biomaterials 2020 05 17;240:119791. Epub 2020 Jan 17.

Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. Electronic address:

In advanced breast cancer (BCa) patients, not the primary tumor, but the development of distant metastases, which occur mainly in the organ bone, and their adverse health effects are responsible for high mortality. Targeted delivery of already known drugs which displayed potency, but rather unfavorable pharmacokinetic properties, might be a promising approach to overcome the current limitations of metastatic BCa therapy. Camptothecin (CPT) is a highly cytotoxic chemotherapeutic compound, yet poorly water-soluble and non-specific. Here, CPT was loaded into porous silicon nanoparticles (pSiNP) displaying the epidermal growth factor receptor (EGFR)-targeting antibody (Ab) cetuximab to generate a soluble and targeted nanoscale delivery vehicle for cancer treatment. After confirming the cytotoxic effect of targeted CPT-loaded pSiNP in vitro on MDA-MB-231BO cells, nanoparticles were studied in a humanized BCa bone metastasis mouse model. Humanized tissue-engineered bone constructs (hTEBCs) provided a humanized microenvironment for BCa bone metastases in female NOD-scid IL2Rg (NSG) mice. Actively targeted CPT-loaded pSiNP led to a reduction of orthotopic primary tumor growth, increased survival rate and significant decrease in hTEBC and murine lung, liver and bone metastases. This study demonstrates that targeted delivery via pSiNP is an effective approach to employ CPT and other potent anti-cancer compounds with poor pharmacokinetic profiles in cancer therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2020.119791DOI Listing
May 2020

Design and Fabrication of Three-Dimensional Printed Scaffolds for Cancer Precision Medicine.

Authors:
Abbas Shafiee

Tissue Eng Part A 2020 03 26;26(5-6):305-317. Epub 2020 Feb 26.

UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, Australia.

Three-dimensional (3D)-engineered scaffolds have been widely investigated as drug delivery systems (DDS) or cancer models with the aim to develop effective cancer therapies. The and models developed via 3D printing (3DP) and tissue engineering concepts have significantly contributed to our understanding of cell-cell and cell-extracellular matrix interactions in the cancer microenvironment. Moreover, 3D tumor models were used to study the therapeutic efficiency of anticancer drugs. The present study aims to provide an overview of applying the 3DP and tissue engineering concepts for cancer studies with suggestions for future research directions. The 3DP technologies being used for the fabrication of personalized DDS have been highlighted and the potential technical approaches and challenges associated with the fused deposition modeling, the inkjet-powder bed, and stereolithography as the most promising 3DP techniques for drug delivery purposes are briefly described. Then, the advances, challenges, and future perspectives in tissue-engineered cancer models for precision medicine are discussed. Overall, future advances in this arena depend on the continuous integration of knowledge from cancer biology, biofabrication techniques, multiomics and patient data, and medical needs to develop effective treatments ultimately leading to improved clinical outcomes. Impact statement Three-dimensional printing (3DP) enables the fabrication of personalized medicines and drug delivery systems. The convergence of 3DP, tissue engineering concepts, and cancer biology could significantly improve our understanding of cancer biology and contribute to the development of new cancer therapies.
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http://dx.doi.org/10.1089/ten.TEA.2019.0278DOI Listing
March 2020

Humanized bone facilitates prostate cancer metastasis and recapitulates therapeutic effects of zoledronic acid in vivo.

Bone Res 2019 21;7:31. Epub 2019 Oct 21.

1Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.

Advanced prostate cancer (PCa) is known for its high prevalence to metastasize to bone, at which point it is considered incurable. Despite significant effort, there is no animal model capable of recapitulating the complexity of PCa bone metastasis. The humanized mouse model for PCa bone metastasis used in this study aims to provide a platform for the assessment of new drugs by recapitulating the human-human cell interactions relevant for disease development and progression. The humanized tissue-engineered bone construct (hTEBC) was created within NOD-scid IL2rg (NSG) mice and was used for the study of experimental PC3-Luc bone metastases. It was confirmed that PC3-Luc cells preferentially grew in the hTEBC compared with murine bone. The translational potential of the humanized mouse model for PCa bone metastasis was evaluated with two clinically approved osteoprotective therapies, the non-species-specific bisphosphonate zoledronic acid (ZA) or the human-specific antibody Denosumab, both targeting Receptor Activator of Nuclear Factor Kappa-Β Ligand. ZA, but not Denosumab, significantly decreased metastases in hTEBCs, but not murine femora. These results highlight the importance of humanized models for the preclinical research on PCa bone metastasis and indicate the potential of the bioengineered mouse model to closely mimic the metastatic cascade of PCa cells to human bone. Eventually, it will enable the development of new effective antimetastatic treatments.
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http://dx.doi.org/10.1038/s41413-019-0072-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804745PMC
October 2019

Microenvironment engineering of osteoblastic bone metastases reveals osteomimicry of patient-derived prostate cancer xenografts.

Biomaterials 2019 11 31;220:119402. Epub 2019 Jul 31.

Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD, Australia; Australian Prostate Cancer Research Centre, Queensland (APCRC-Q), QUT, Brisbane, QLD, Australia; Translational Research Institute (TRI), QUT, Brisbane, QLD, Australia; Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove, QLD, Australia; School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, Australia. Electronic address:

Representative in vitro models that mimic the native bone tumor microenvironment are warranted to support the development of more successful treatments for bone metastases. Here, we have developed a primary cell 3D model consisting of a human osteoblast-derived tissue-engineered construct (hOTEC) indirectly co-cultured with patient-derived prostate cancer xenografts (PDXs), in order to study molecular interactions in a patient-derived microenvironment context. The engineered biomimetic microenvironment had high mineralization and embedded osteocytes, and supported a high degree of cancer cell osteomimicry at the gene, protein and mineralization levels when co-cultured with prostate cancer PDXs from a lymph node metastasis (LuCaP35) and bone metastasis (BM18) from patients with primary prostate cancer. This fully patient-derived model is a promising tool for the assessment of new molecular mechanisms and as a personalized pre-clinical platform for therapy testing for patients with prostate cancer bone metastases.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119402DOI Listing
November 2019

Recombinant Human Bone Morphogenetic Protein 7 Exerts Osteo-Catabolic Effects on Bone Grafts That Outweigh Its Osteo-Anabolic Capacity.

Calcif Tissue Int 2019 09 18;105(3):331-340. Epub 2019 Jun 18.

Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia.

This study aimed to investigate the effects of recombinant human bone morphogenetic protein (rhBMP-7) on human cancellous bone grafts (BGs) while differentiating between anabolic and catabolic events. Human BGs alone or supplemented with rhBMP-7 were harvested 14 weeks after subcutaneous implantation into NOD/Scid mice, and studied via micro-CT, histomorphometry, immunohistochemistry and flow cytometry. Immunohistochemical staining for human-specific proteins made it possible to differentiate between grafted human bone and newly formed murine bone. Only BGs implanted with rhBMP-7 formed an ossicle containing a functional hematopoietic compartment. The total ossicle volume in the BMP group was higher than in the BMP group (835 mm vs. 365 mm, respectively, p < 0.001). The BMP group showed larger BM spaces (0.47 mm vs. 0.28 mm, p = 0.002) and lower bone volume-to-total volume ratio (31% vs. 47%, p = 0.002). Immunohistochemical staining for human-specific proteins confirmed a higher ratio of newly formed bone area (murine) to total area (0.12 vs. 0.001, p < 0.001) in the BMP+ group, while the ratio of grafted bone (human) area to total area was smaller (0.14 vs. 0.34, p = 0.004). The results demonstrate that rhBMP-7 induces BG resorption at a higher rate than new bone formation while creating a haematopoietic niche. Clinicians therefore need to consider the net catabolic effect when rhBMP-7 is used with BGs. Overall, this model indicates its promising application to further decipher BMPs action on BGs and its potential in complex bone tissue regeneration.
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http://dx.doi.org/10.1007/s00223-019-00574-5DOI Listing
September 2019

3D printed dual macro-, microscale porous network as a tissue engineering scaffold with drug delivering function.

Biofabrication 2019 04 26;11(3):035014. Epub 2019 Apr 26.

ARC Centre in Additive Biomanufacturing, Queensland University of Technology (QUT), Brisbane, Queensland, Australia. Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, QUT, Brisbane, Queensland, Australia.

Tissue engineering macroporous scaffolds are important for regeneration of large volume defects resulting from diseases such as breast or bone cancers. Another important part of the treatment of these conditions is adjuvant drug therapy to prevent disease recurrence or surgical site infection. In this study, we developed a new type of macroporous scaffolds that have drug loading and release functionality to use in these scenarios. 3D printing allows for building macroporous scaffolds with deterministically designed complex architectures for tissue engineering yet they often have low surface areas thus limiting their drug loading capability. In this proof-of-concept study, we aimed to introduce microscale porosity into macroporous scaffolds to allow for efficient yet simple soak-loading of various clinical drugs and control their release. Manufacturing of scaffolds having both macroporosity and microscale porosity remains a difficult task. Here, we combined porogen leaching and 3D printing to achieve this goal. Porogen microparticles were mixed with medical grade polycaprolactone and extruded into scaffolds having macropores of 0.7 mm in size. After leaching, intra-strut microscale pores were realized with pore size of 20-70 μm and a total microscale porosity of nearly 40%. Doxorubicin (DOX), paclitaxel (PTX) and cefazolin (CEF) were chosen as model drugs of different charges and solubilities to soak-load the scaffolds and achieved loading efficiency of over 80%. The microscale porosity was found to significantly reduce the burst release allowing the microporous scaffolds to release drugs up to 200, 500 and 150 h for DOX, PTX and CEF, respectively. Finally, cell assays were used and confirmed the bioactivities and dose response of the drug-loaded scaffolds. Together, the findings from this proof-of-concept study demonstrate a new type of scaffolds with dual micro-, macro-porosity for tissue engineering applications with intrinsic capability for efficient loading and sustained release of drugs to prevent post-surgery complications.
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http://dx.doi.org/10.1088/1758-5090/ab14ffDOI Listing
April 2019

Humanization of the Prostate Microenvironment Reduces Homing of PC3 Prostate Cancer Cells to Human Tissue-Engineered Bone.

Cancers (Basel) 2018 Nov 13;10(11). Epub 2018 Nov 13.

Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia.

The primary tumor microenvironment is inherently important in prostate cancer (PCa) initiation, growth and metastasis. However, most current PCa animal models are based on the injection of cancer cells into the blood circulation and bypass the first steps of the metastatic cascade, hence failing to investigate the influence of the primary tumor microenvironment on PCa metastasis. Here, we investigated the spontaneous metastasis of PC3 human PCa cells from humanized prostate tissue, containing cancer-associated fibroblasts (CAFs) and prostate lymphatic and blood vessel endothelial cells (BVEC), to humanized tissue-engineered bone constructs (hTEBC) in NOD-SCID IL2Rγ (NSG) mice. The hTEBC formed a physiologically mature organ bone which allowed homing of metastatic PCa cells. Humanization of prostate tissue had no significant effect on the tumor burden at the primary site over the 4 weeks following intraprostatic injection, yet reduced the incidence and burden of metastases in the hTEBC. Spontaneous PCa metastases were detected in the lungs and spleen with no significant differences between the humanized and non-humanized prostate groups. A significantly greater metastatic tumor burden was observed in the liver when metastasis occurred from the humanized prostate. Together, our data suggests that the presence of human-derived CAFs and BVECs in the primary PCa microenvironment influences selectively the metastatic and homing behavior of PC3 cells in this model. Our orthotopic and humanized prostate cancer model developed via convergence of cancer research and tissue engineering concepts provides an important platform to study species-specific PCa bone metastasis and to develop and test therapeutic strategies.
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http://dx.doi.org/10.3390/cancers10110438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265886PMC
November 2018

Immunosuppression Agent Cyclosporine Reduces Self-Renewal and Vessel Regeneration Potentiation of Human Endothelial Colony Forming Cells.

Stem Cells Transl Med 2019 02 13;8(2):162-168. Epub 2018 Oct 13.

UQ Diamantina Institute, The University of Queensland, Brisbane, Queensland, Australia.

Endothelial colony forming cells (ECFC) and mesenchymal stem cells (MSC) combined have great potential to be used for cell therapy of ischemic vascular diseases. However, to improve allogeneic stem cell engraftment the use of immunosuppression, such as cyclosporine has been suggested. Our aim was to assess the impact of cyclosporine on hind limb revascularisation upon MSC and ECFC combination therapy. Balb/c immunocompetent mice subjected to hind limb ischemia (right femoral artery ligation) were given both human ECFC and MSC (weekly intramuscular injections) with or without cyclosporine (daily injection). Surprisingly, mice receiving cyclosporine had a significant decrease in reperfusion based on laser Doppler imaging compared to vehicle controls and had poorer limb survival. In vitro, the downstream calcineurin target NFATC4 was highly expressed in the self-renewing fraction of ECFCs. ECFCs cultured with cyclosporine had reduced colony formation capacity and tube formation in Matrigel. Lastly, ECFC displayed increased proliferation and loss of capacity for long term culture when in the presence of cyclosporine clearly showing a loss of quiescence and progenitor function. Our findings demonstrate the deleterious impact of cyclosporine on ECFC function, with significant impact on ECFC-based allogeneic cellular therapy. Stem Cells Translational Medicine 2019;8:162&7.
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http://dx.doi.org/10.1002/sctm.18-0103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344910PMC
February 2019

Humanization of bone and bone marrow in an orthotopic site reveals new potential therapeutic targets in osteosarcoma.

Biomaterials 2018 07 16;171:230-246. Epub 2018 Apr 16.

Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, QLD 4059, Brisbane, Australia; George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive Northwest, Atlanta, GA 30332, USA; Institute for Advanced Study, Technical University Munich, Lichtenbergstraße 2a, 85748 Garching, Munich, Germany. Electronic address:

Background: Existing preclinical murine models often fail to predict effects of anti-cancer drugs. In order to minimize interspecies-differences between murine hosts and human bone tumors of in vivo xenograft platforms, we tissue-engineered a novel orthotopic humanized bone model.

Methods: Orthotopic humanized tissue engineered bone constructs (ohTEBC) were fabricated by 3D printing of medical-grade polycaprolactone scaffolds, which were seeded with human osteoblasts and embedded within polyethylene glycol-based hydrogels containing human umbilical vein endothelial cells (HUVECs). Constructs were then implanted at the femur of NOD-scid and NSG mice. NSG mice were then bone marrow transplanted with human CD34  cells. Human osteosarcoma (OS) growth was induced within the ohTEBCs by direct injection of Luc-SAOS-2 cells. Tissues were harvested for bone matrix and marrow morphology analysis as well as tumor biology investigations. Tumor marker expression was analyzed in the humanized OS and correlated with the expression in 68 OS patients utilizing tissue micro arrays (TMA).

Results: After harvesting the femurs micro computed tomography and immunohistochemical staining showed an organ, which had all features of human bone. Around the original mouse femur new bone trabeculae have formed surrounded by a bone cortex. Staining for human specific (hs) collagen type-I (hs Col-I) showed human extracellular bone matrix production. The presence of nuclei staining positive for human nuclear mitotic apparatus protein 1 (hs NuMa) proved the osteocytes residing within the bone matrix were of human origin. Flow cytometry verified the presence of human hematopoietic cells. After injection of Luc-SAOS-2 cells a primary tumor and lung metastasis developed. After euthanization histological analysis showed pathognomic features of osteoblastic OS. Furthermore, the tumor utilized the previously implanted HUVECS for angiogenesis. Tumor marker expression was similar to human patients. Moreover, the recently discovered musculoskeletal gene C12orf29 was expressed in the most common subtypes of OS patient samples.

Conclusion: OhTEBCs represent a suitable orthotopic microenvironment for humanized OS growth and offers a new translational direction, as the femur is the most common location of OS. The newly developed and validated preclinical model allows controlled and predictive marker studies of primary bone tumors and other bone malignancies.
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http://dx.doi.org/10.1016/j.biomaterials.2018.04.030DOI Listing
July 2018

N-arylmethylideneaminophthalimide: Design, Synthesis and Evaluation as Analgesic and Anti-inflammatory Agents.

Mini Rev Med Chem 2019 ;19(8):679-687

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Research Center, Tehran University of Medical Sciences, Iran.

Background And Objective: N-aryl derivatives of phthalimide and 4-nitro phthalimide have demonstrated cyclooxygenase inhibitory activity. Also, they possess excellent analgesic and antiinflammatory activity. In this work, a new series of N-arylmethylideneamino derivatives of phthalimide and 4-nitro phthalimide were designed and synthesized.

Methods: The designed compounds were synthesized by condensation of the appropriate aldehyde and N-aminophthalimide in ethanol at room temperature at PH around 3. Their analgesic and antiinflammatory activity were evaluated by acetic acid-induced pain test and carrageenan-induced paw edema test in mice and rats, respectively.

Results And Conclusion: The details of the synthesis and chemical characterization of the analogs are described. In vivo screening showed compounds 3a, 3b, 3f and 3h were the most potent analgesic compounds. In addition, compounds 3a, 3c, 3d, 3e and 3j indicated comparable anti-inflammatory activity to indomethacin as a reference drug.
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http://dx.doi.org/10.2174/1389557518666180424101009DOI Listing
June 2019

Immune system augmentation via humanization using stem/progenitor cells and bioengineering in a breast cancer model study.

Int J Cancer 2018 09 7;143(6):1470-1482. Epub 2018 May 7.

Institute of Health and Biomedical Innovation, Centre for Regenerative Medicine, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, QLD 4059, Brisbane, Australia.

Despite significant advances, most current in vivo models fail to fully recapitulate the biological processes that occur in humans. Here we aimed to develop an advanced humanized model with features of an organ bone by providing different bone tissue cellular compartments including preosteoblasts, mesenchymal stem/stromal (MSCs), endothelial and hematopoietic cells in an engineered microenvironment. The bone compartment was generated by culturing the human MSCs, umbilical vein endothelial cells with gelatin methacryloyl hydrogels in the center of a melt-electrospun polycaprolactone tubular scaffolds, which were seeded with human preosteoblasts. The tissue engineered bone (TEB) was subcutaneously implanted into the NSG mice and formed a morphologically and functionally organ bone. Mice were further humanized through the tail vein injection of human cord blood derived CD34+ cells, which then populated in the mouse bone marrow, spleen and humanized TEB (hTEB). 11 weeks after CD34+ transplantation, metastatic breast cancer cells (MDA-MB-231BO) were orthotopically injected. Cancer cell injection resulted in the formation of a primary tumor and metastasis to the hTEB and mouse organs. Less frequent metastasis and lower tumor burden were observed in hematochimeric mice, suggesting an immune-mediated response against the breast cancer cells. Overall, our results demonstrate the efficacy of tissue engineering approaches to study species-specific cancer-bone interactions. Further studies using genetically modified hematopoietic stem cells and bioengineered microenvironments will enable us to address the specific roles of signaling molecules regulating hematopoietic niches and cancer metastasis in vivo.
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http://dx.doi.org/10.1002/ijc.31528DOI Listing
September 2018

Aspartic acid functionalized PEGylated MSN@GO hybrid as an effective and sustainable nano-system for in-vitro drug delivery.

Adv Med Sci 2018 Sep 20;63(2):257-264. Epub 2018 Mar 20.

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: In this research, aspartic acid functionalized PEGylated mesoporous silica nanoparticlesgraphene oxide nanohybrid (As-PEGylated-MSN@GO) prepared as a pH-responsive drug carrier for the curcumin delivery. For better camouflage during blood circulation, poly(ethylene glycol) was decorated on the surface of MSN@GO nanohybrid.

Materials And Methods: The nanocarrier was characterized by using X-ray powder diffraction (XRD), dynamic light scattering (DLS), UV-vis spectroscopy, thermal gravimetry analysis (TGA), FT-IR, SEM and TEM.

Results: The size of modified MSN@GO was around 75.8 nm and 24% wt. of curcumin was loaded on the final nanohybrid. pHdecrement from 7.4 to 5.8 the release medium led to increase the cumulative amount of drug release from 54% to 98%.

Conclusions: As-functionalized MSN@GO had no cytotoxicity against human breast adenocarcinoma (MCF-7) and human mammary epithelial (MCF10A) as cancerous and normal cell lines, respectively. Whereas curcuminloaded nanohybrid showed excellent killing capability against MCF-7 cells.
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http://dx.doi.org/10.1016/j.advms.2018.01.003DOI Listing
September 2018

Meso-Endothelial Bipotent Progenitors from Human Placenta Display Distinct Molecular and Cellular Identity.

Stem Cell Reports 2018 03 1;10(3):890-904. Epub 2018 Mar 1.

UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia; UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD, Australia. Electronic address:

The existence of bipotential precursors for both mesenchymal and endothelial stem/progenitor cells in human postnatal life is debated. Here, we hypothesized that such progenitors are present within the human term placenta. From a heterogeneous placental single-cell suspension, a directly flow-sorted CD45CD34CD144CD31Lo population uniquely differentiated into both endothelial and mesenchymal colonies in limiting dilution culture assays. Of interest, these bipotent cells were in vessel walls but not in contact with the circulation. RNA sequencing and functional analysis demonstrated that Notch signaling was a key driver for endothelial and bipotential progenitor function. In contrast, the formation of mesenchymal cells from the bipotential population was not affected by TGFβ receptor inhibition, a classical pathway for endothelial-mesenchymal transition. This study reveals a bipotent progenitor phenotype in the human placenta at the cellular and molecular levels, giving rise to endothelial and mesenchymal cells ex vivo.
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http://dx.doi.org/10.1016/j.stemcr.2018.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918195PMC
March 2018

Polyoxometalate-metal organic framework-lipase: An efficient green catalyst for synthesis of benzyl cinnamate by enzymatic esterification of cinnamic acid.

Int J Biol Macromol 2018 Jul 15;113:8-19. Epub 2018 Feb 15.

Institute of Nano Science and NanoTechnology, Razi University, Kermanshah 67149, Iran; Department of Inorganic Chemistry, Faculty of Chemistry, Razi University, Kermanshah 67149, Iran. Electronic address:

Iron-carboxylate (MIL-100(Fe)) and HKUST-1 (Cu(BTC), BTC=1,3,5-benzenetricarboxylic acid) as nanoporous metal organic framework supports were compared for immobilization of porcine pancreatic lipase (PPL). These immobilizations improved thermal, pH and operational stability of PPL compared to the soluble enzyme. Stability of MIL-100(Fe) was better than HKUST-1 as support. MIL-100(Fe) encapsulated Keggin phosphotungstic acid HPWO (PW) (PW@MIL-100(Fe)) was synthesized to develop novel enzyme immobilized system and characterized by Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD) and Barrett Joyner Halenda (BJH) analysis. Relative activity for immobilized lipase on PW@MIL-100(Fe) was more than MIL-100(Fe) in pH range of 3-9. At the elevated temperature of 70°C, the PW@MIL-100(Fe) was the most stable one. PW@MIL-100(Fe)/PPL substrate exhibited the higher stability at 4°C and 25°C, along with other supports. Moreover, PW@MIL-100(Fe) was chosen as the best support for immobilization of PPL and was also applied for the synthesis of benzyl cinnamate by enzymatic esterification of cinnamic acid. The immobilized enzyme retained 90.4% of its initial activity during synthesis of benzyl cinnamate after 5 successive catalytic rounds and reached 80.0% yield after 8 reuses.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.02.023DOI Listing
July 2018

Anticonvulsant Effects of New 1, 4-DihydropyridineDerivatives Containing Imidazolyl Moiety Against Seizures Induced by Pentylenetetrazole and Maximal Electroshock in Mice.

Iran J Pharm Res 2017 ;16(3):893-903

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Epilepsy is a chronic disorder of the brain affecting around 50 million people in the world. Up to 30% of epileptic patients do not respond to available drugs and medical therapies. In this paper, anticonvulsant screening of 10 synthesized new derivatives of 1, 4-dihydropyridine-3, 5-dicarboxamides was performed. Anticonvulsant activity was evaluated by intravenous and intraperitoneal pentylenetetrazole and maximal electroshock induced seizures tests. Nifedipine was used as reference drug. Our pharmacological results revealing the compounds 2, 4, 5, and 6 can be effective in both absence and grandmal seizures in human. These pharmacological studies have displayed that these new dihydropyridine derivatives are capable to inhibiting seizures induced by pentylenetetrazole and maximal electroshock in mice efficiently.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610745PMC
January 2017

Mesenchymal stem/stromal cells enhance engraftment, vasculogenic and pro-angiogenic activities of endothelial colony forming cells in immunocompetent hosts.

Sci Rep 2017 10 19;7(1):13558. Epub 2017 Oct 19.

The University of Queensland, UQ Centre for Clinical Research, Brisbane, 4029, QLD, Australia.

The clinical use of endothelial colony forming cells (ECFC) is hampered by their restricted engraftment. We aimed to assess engraftment, vasculogenic and pro-angiogenic activities of ECFC in immunocompetent (C57BL/6: WT) or immunodeficient (rag1 C57BL/6: Rag1) mice. In addition, the impact of host immune system was investigated where ECFC were co-implanted with mesenchymal stem/stromal cells (MSC) from adult bone marrow (AdBM-MSC), fetal bone marrow (fBM-MSC), fetal placental (fPL-MSC), or maternal placental (MPL-MSC). Transplantation of ECFCs in Matrigel plugs resulted in less cell engraftment in WT mice compared to Rag1 mice. Co-implantation with different MSCs resulted in a significant increase in cell engraftment up to 9 fold in WT mice reaching levels of engraftment observed when using ECFCs alone in Rag1 mice but well below levels of engraftment with MSC-ECFC combination in Rag1 recipients. Furthermore, MSCs did not reduce murine splenic T cell proliferation in response to ECFCs in vitro. ECFCs enhanced the murine neo-vascularization through paracrine effect, but with no difference between Rag1 and WT mice. In conclusions, the host adaptive immune system affects the engraftment of ECFCs. MSC co-implantation improves ECFC engraftment and function even in immunocompetent hosts mostly through non-immune mechanisms.
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http://dx.doi.org/10.1038/s41598-017-13971-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648925PMC
October 2017

In Silico Screening of IL-1β Production Inhibitors Using Chemometric Tools.

Iran J Pharm Res 2017 ;16(2):513-524

Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

The IL-1β plays a major role in inflammatory disorders and IL-1β production inhibitors can be used in the treatment of inflammatory and related diseases. In this study, quantitative relationships between the structures of 46 pyridazine derivatives (inhibitors of IL-1β production) and their activities were investigated by Multiple Linear Regression (MLR) technique Stepwise Regression Method (ES-SWR). The genetic algorithm (GA) has been proposed for improvement of the performance of the MLR modeling by choosing the most relevant descriptors. The results show that eight descriptors are able to describe about 83.70% of the variance in the experimental activity of the molecules in the training set. The physical meaning of the selected descriptors is discussed in detail. Power predictions of the QSAR models developed were evaluated using cross-validation, and validation through an external prediction set. The results showed satisfactory goodness-of-fit, robustness and perfect external predictive performance. The applicability domain was used to define the area of reliable predictions. Furthermore, the screening technique was applied in order to predict the structure and potency of new compounds of this type using the proposed QSAR model.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603860PMC
January 2017

Coumarin derivatives bearing benzoheterocycle moiety: synthesis, cholinesterase inhibitory, and docking simulation study.

Iran J Basic Med Sci 2017 Jun;20(6):631-638

Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: To investigate the efficiency of a novel series of coumarin derivatives bearing benzoheterocycle moiety as novel cholinesterase inhibitors.

Materials And Methods: Different 7-hydroxycoumarin derivatives were synthesized via Pechmann or Knoevenagel condensation and conjugated to different benzoheterocycle (8-hydroxyquinoline, 2-mercaptobenzoxazole or 2-mercaptobenzimidazole) using dibromoalkanes 3a-m: Final compounds were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by Ellman's method. Kinetic study of AChE inhibition and ligand-protein docking simulation were also carried out for the most potent compound 3b.

Results: Some of the compounds revealed potent and selective activity against AChE. Compound 3b containing the quinoline group showed the best activity with an IC value of 8.80 μM against AChE. Kinetic study of AChE inhibition revealed the mixed-type inhibition of the enzyme by compound 3b. Ligand-protein docking simulation also showed that the flexibility of the hydrophobic five carbons linker allows the quinoline ring to form π-π interaction with Trp279 in the PAS.

Conclusion: We suggest these synthesized compounds could become potential leads for AChE inhibition and prevention of AD symptoms.
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http://dx.doi.org/10.22038/IJBMS.2017.8830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569448PMC
June 2017

Fetal Bone Marrow-Derived Mesenchymal Stem/Stromal Cells Enhance Humanization and Bone Formation of BMP7 Loaded Scaffolds.

Biotechnol J 2017 Dec 25;12(12). Epub 2017 Sep 25.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.

Tissue engineered constructs built with human cells capable of generating a bone-like organ within the mouse have attracted considerable interest over the past decade. Here, we aimed to compare the utility of human mesenchymal stem/stromal cells (MSC) isolated from fetal term placenta (fPL-MSC) and fetal first trimester bone marrow (fBM-MSC) in a polycaprolactone scaffold/BMP7-based model in nude mice. Furthermore, fPL-MSC were co-seeded with fetal placenta-derived endothelial colony forming cells (ECFC) to assess the impact of ECFC on fPL-MSC osteogenesis. X-ray radiography and micro computed tomography analyses showed enhanced bone formation in all BMP7 groups; however there was no difference after 2 months in bone formation between scaffolds seeded with fPL-MSC alone or combination of ECFC and fPL-MSC. Of interest, fBM-MSC showed the highest level of bone formation. Additionally, endochondral ossification contributed in generation of bone in fBM-MSC. Histological analysis showed the primary role of BMP in generation of cortical and trabecular bone, and the recruitment of hematopoietic cells to the scaffolds. Current in vivo engineered bone organs can potentially be used for drug screening or as models to study bone tissue development in combination with haematopoiesis.
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http://dx.doi.org/10.1002/biot.201700414DOI Listing
December 2017

Avoidance of Maternal Cell Contamination and Overgrowth in Isolating Fetal Chorionic Villi Mesenchymal Stem Cells from Human Term Placenta.

Stem Cells Transl Med 2017 04 16;6(4):1070-1084. Epub 2017 Feb 16.

The University of Queensland, UQ Centre for Clinical Research, Experimental Fetal Medicine Group, Herston, Queensland, Australia.

Human placenta is rich in mesenchymal stem/stromal cells (MSC), with their origin widely presumed fetal. Cultured placental MSCs are confounded by a high frequency of maternal cell contamination. Our recent systematic review concluded that only a small minority of placental MSC publications report fetal/maternal origin, and failed to discern a specific methodology for isolation of fetal MSC from term villi. We determined isolation conditions to yield fetal and separately maternal MSC during ex vivo expansion from human term placenta. MSCs were isolated via a range of methods in combination; selection from various chorionic regions, different commercial media, mononuclear cell digest and/or explant culture. Fetal and maternal cell identities were quantitated in gender-discordant pregnancies by XY chromosome fluorescence in situ hybridization. We first demonstrated reproducible maternal cell contamination in MSC cultures from all chorionic anatomical locations tested. Cultures in standard media rapidly became composed entirely of maternal cells despite isolation from fetal villi. To isolate pure fetal cells, we validated a novel isolation procedure comprising focal dissection from the cotyledonary core, collagenase/dispase digestion and explant culture in endothelial growth media that selected, and provided a proliferative environment, for fetal MSC. Comparison of MSC populations within the same placenta confirmed fetal to be smaller, more osteogenic and proliferative than maternal MSC. We conclude that in standard media, fetal chorionic villi-derived MSC (CV-MSC) do not grow readily, whereas maternal MSC proliferate to result in maternal overgrowth during culture. Instead, fetal CV-MSCs require isolation under specific conditions, which has implications for clinical trials using placental MSC. Stem Cells Translational Medicine 2017;6:1070-1084.
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http://dx.doi.org/10.1002/sctm.15-0327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442838PMC
April 2017