Publications by authors named "Senthilkumar Preethy"

25 Publications

  • Page 1 of 1

A 3D Polymer Scaffold Platform for Enhanced Culture of Human & Rabbit Buccal Epithelial Cells for Cell Therapies.

Tokai J Exp Clin Med 2021 Apr 20;46(1):1-6. Epub 2021 Apr 20.

II Department of Surgery & Center for Advancing Clinical Research (CACR), University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi 409-3898, Japan.

Background: Buccal mucosal epithelial cells show promising application for various regenerative medicine approaches. In this study, we examined the feasibility of culturing rabbit and human buccal mucosal epithelial cells in a novel thermoreversible gelation polymer (TGP) scaffold, without feeder layers or other foreign proteins.

Methods & Results: The results of this 28-day culture, u sing the conventional technique (2D) and TGP (3D) showed that the epithelial cell morphology could be maintained only in the TGP group while cells in the 2D group de-differentiated to fibroblast morphology in both human and rabbit samples. CK3 expression, a marker for epithelial differentiation was higher in 3D-TGP cultured cells than 2D.

Conclusion: TGP based cell culture is a prospective methodology to culture buccal mucosal epithelial cells efficiently without using foreign biological components for tissue engineering applications.
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April 2021

A novel human donor cornea preservation cocktail incorporating a thermo-reversible gelation polymer (TGP), enhancing the corneal endothelial cell density maintenance and explant culture of corneal limbal cells.

Biotechnol Lett 2021 Mar 25. Epub 2021 Mar 25.

Centre for Advancing Clinical Research (CACR), Faculty of Medicine, Yamanashi University, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.

Purpose: McCarey-Kaufman's (MK) medium and Optisol-GS medium are the most commonly employed media for human donor corneal preservation. In this study, we evaluated the preservation efficacy of discarded human donor corneas using a Thermo-reversible gelation polymer (TGP) added to these two media.

Methods: Thirteen human corneal buttons collected from deceased donors, which were otherwise discarded due to low endothelial cell density (ECD) were used. They were stored in four groups: MK medium, MK medium with TGP, Optisol-GS and Optisol-GS with TGP at 4 °C for 96 h. Slit lamp examination and specular microscopy were performed. Corneal limbal tissues from these corneas were then cultured using explant methodology one with and the other without TGP scaffold, for 21 days.

Results: MK + TGP and Optisol-GS + TGP preserved corneas better than without TGP, which was observed by maintenance of ECD which was significantly higher in Optisol-GS + TGP than MK + TGP (p-value = 0.000478) and corneal thickness remaining the same for 96 h. Viable corneal epithelial cells could be grown from the corneas stored only in MK + TGP and Optisol-GS + TGP. During culture, the TGP scaffold helped maintain the native epithelial phenotype and progenitor/stem cell growth was confirmed by RT-PCR characterization.

Conclusion: TGP reconstituted with MK and Optisol-GS media yields better preservation of human corneal buttons in terms of relatively higher ECD maintenance and better in vitro culture outcome of corneal limbal tissue. This method has the potential to become a standard donor corneal transportation-preservation methodology and it can also be extended to other tissue or organ transportation upon further validation.
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http://dx.doi.org/10.1007/s10529-021-03116-yDOI Listing
March 2021

Enhanced expression of hyaluronic acid in osteoarthritis-affected knee-cartilage chondrocytes during three-dimensional in vitro culture in a hyaluronic-acid-retaining polymer scaffold.

Knee 2021 Mar 6;29:365-373. Epub 2021 Mar 6.

II Department of Surgery & CACR, Yamanashi University-Faculty of Medicine, Yamanashi, Japan; The Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, Tamil Nadu, India; JBM Inc., Edogawa-Ku, Tokyo, Japan; GN Corporation Co. Ltd., Yamanashi, Japan. Electronic address:

Background: Chondrocyte transplantation to address cartilage damage is an established solution. Because hyaluronic acid (HA) is an essential component for homeostasis of the cartilage, in order to arrive at methodologies to utilize its advantages in cell-based therapies, we compared the HA retention capability of a thermoreversible gelation polymer scaffold-based environment (3D-TGP) with conventional in vitro cell culture methodologies.

Methods: Chondrocytes derived from osteoarthritis-affected knee joint cartilage of elderly patients were used and accomplished in three phases. In Phase I, the levels of HA secreted by chondrocytes were measured in culture supernatant. In Phase II, retention capacity of externally added HA was quantified indirectly by measuring the HA released in culture supernatant, and in Phase III, the expression of CD44 on cells was analysed by immunohistochemistry.

Results: In Phase I, the average HA in the 3D supernatant was 3% that of 2D. In phase II, 80% of externally added HA was detected in the 2D on day 7, while in 3D-TGP, only 0.1% was released until day 21. In Phase III, 2D yielded individual cells that started degenerating from the third week; in 3D-TGP cells grew for a longer duration, formed a tissue-like architecture with extracellular matrix with significantly intense staining of CD44 than 2D.

Conclusion: The capability of the 3D-TGP culture environment to retain HA and support chondrocytes to grow with a tissue-like architecture expressing higher HA content is considered advantageous as it serves as an in vitro culture platform that enables tissue engineering of cartilage tissue with native hyaline phenotype and higher HA expression. The in vitro environment being conducive, based on this data, we also recommend that the TGP be tried as an encapsulation material in clinical studies of chondrocyte implantation for optimal clinical outcome.
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http://dx.doi.org/10.1016/j.knee.2021.02.019DOI Listing
March 2021

β-glucans: wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach to COVID-19.

Hum Vaccin Immunother 2021 Mar 2:1-6. Epub 2021 Mar 2.

The Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India.

Conventional vaccines to combat COVID-19 through different approaches are at various stages of development. The complexity of COVID-19 such as the potential mutations of the virus leading to antigenic drift and the uncertainty on the duration of the immunity induced by the vaccine have hampered the efforts to control the COVID-19 pandemic. Thus, we suggest an alternative interim treatment strategy based on biological response modifier glucans such as the AFO-202-derived β-glucan, which has been reported to induce trained immunity, akin to that induced by the Bacille Calmette-Guérin vaccine, by epigenetic modifications at the central level in the bone marrow. These β-glucans act as pathogen-associated molecular patterns, activating mucosal immunity by binding with specific pathogen recognition receptors such as dectin-1 and inducing both the adaptive and innate immunity by reaching distant lymphoid organs. β-Glucans have also been used as immune adjuvants for vaccines such as the influenza vaccine. Therefore, until a conventional vaccine is widely available, an orally consumable vaccine adjuvant that acts like biosimilars, termed as the wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach, with well-reported safety is worth in-depth investigation and can be considered for a clinical trial.
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http://dx.doi.org/10.1080/21645515.2021.1880210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938654PMC
March 2021

A three-dimensional in vitro culture environment of a novel polymer scaffold, yielding chondroprogenitors and mesenchymal stem cells in human chondrocytes derived from osteoarthritis-affected cartilage tissue.

J Orthop 2021 Jan-Feb;23:138-141. Epub 2021 Jan 16.

Centre for Advancing Clinical Research (CACR), University of Yamanashi -Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.

Objective: We evaluated the expression of stem/progenitor biomarkers in osteoarthritic tissue derived chondrocytes cultured using a three-dimensional (3D) thermo-reversible gelation polymer (TGP).

Methods: The chondrocytes from discarded biopsy tissues obtained from human elderly patients with osteoarthritis were cultured using the 3D-TGP up to six weeks.

Results: The chondrocytes grew in a tissue-like manner, without de-differentiation into fibroblasts, and the cells thus tissue-engineered were proven positive for CD49e, OCT4, CD-105 and STRO-1 by immunohistochemistry.

Conclusion: This study establishes the efficacy of this 3D-TGP platform for clinically useable tissue-engineered cartilage for improvising the clinical outcome of cell therapy for cartilage repair.
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http://dx.doi.org/10.1016/j.jor.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815488PMC
January 2021

Potential of combination of bone marrow nucleated and mesenchymal stem cells in complete spinal cord injury.

Curr Stem Cell Res Ther 2020 Oct 29. Epub 2020 Oct 29.

Edogawa Evolutionary Laboratory of Science (EELS), Edogawa Hospital, 2-24-18 Higashikoiwa, Edogawa, 133-0052, Tokyo. Japan.

Background: Cell-based therapies represent one of the definitive treatment approaches to SCI which to become a routine clinical application is marred by several known unknowns. The bone marrow mononuclear cells (BMMNCs) and mesenchymal stem cells (MSCs) represent the most clinically applied cell types for SCI in humans, with safety established and to an extent, efficacy reported.

Methods: In this review we have analysed the clinical studies done using BMMNC and MSC for complete SCI separately and the potential for applying those cells in combination. We have also analysed those factors whose outcome in animal studies of SCI could be evaluated in depth but the clinical outcome cannot be evaluated intrinsically owing to practical difficulties.

Conclusion: A combination of these two cell types, BMMNC and MSC has been proven to be advantageous than applying them separately. Therefore, a thorough evaluation including rationale and potential implications of applying these two therapies has been presented here and we hypothesize that such a combination is likely to improvise the outcome of a wholesome approach to spinal cord regeneration after SCI.
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http://dx.doi.org/10.2174/1574888X15666201029160542DOI Listing
October 2020

Coagulopathy associated with COVID-19 - Perspectives & Preventive strategies using a biological response modifier Glucan.

Thromb J 2020 16;18:27. Epub 2020 Oct 16.

II Department of Surgery & Centre for Advancing Clinical Research (CACR), Yamanashi University- School of Medicine, Chuo, Japan.

Direct endothelial injury by viruses and dysregulation of clotting mechanisms due to cytokine storm are the major precipitating factors of mortality in COVID-19; both are attributed to a fundamental dysregulation of the immune system. While immune dysregulation can be attributed to several factors, the risk of associated thrombogenic disruption varies across individuals. This variation depends on several factors, such as comorbidities, including diabetes, hypertension, and cardiovascular diseases. When considering ethnic variations, the vulnerability of Caucasians, African Americans and Hispanics needs to be addressed before arriving at strategies to handle thromboembolic complications, which have been identified in recent reports as the leading causes of mortality in COVID-19. Although evaluation of D-dimer and prothrombin during admission is considered to predict prognosis and mortality, there are no preventive or prophylactic strategies before hospital admission. Herein, we present our perspectives on the effect of regular supplementation with the biological response modifier beta glucan based on its relevance to immune modulation. This effect is of paramount importance in decreasing the development of severe COVID-19 and reducing mortality against the background of coagulopathy, especially in vulnerable populations.
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http://dx.doi.org/10.1186/s12959-020-00239-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563912PMC
October 2020

Role of Immune Dysregulation in Increased Mortality Among a Specific Subset of COVID-19 Patients and Immune-Enhancement Strategies for Combatting Through Nutritional Supplements.

Front Immunol 2020 9;11:1548. Epub 2020 Jul 9.

The Mary-Yoshio Translational Hexagon, Nichi-In Centre for Regenerative Medicine, Chennai, India.

The COVID-19 pandemic has been causing varying severities of illness. Some are asymptomatic and some develop severe disease leading to mortality across ages. This contrast triggered us explore the causes, with the background that a vaccine for effective immunization or a drug to tackle COVID-19 is not too close to reality. We have discussed strategies to combat COVID-19 through immune enhancement, using simple measures including nutritional supplements. A literature search on mortality-related comorbid conditions was performed. For those conditions, we analyzed the pro-inflammatory cytokines, which could cause the draining of the immune reservoir. We also analyzed the immune markers necessary for the defense mechanism/immune surveillance against COVID-19, especially through simple means including immune enhancing nutritional supplement consumption, and we suggest strategies to combat COVID-19. Major comorbid conditions associated with increased mortality include cardiovascular disease (CVD), diabetes, being immunocompromised by cancer, and severe kidney disease with a senile immune system. Consumption of strain (AFO-202) beta 1,3-1,6 glucan supported enhanced IL-8, sFAS macrophage activity, and NK cells' cytotoxicity, which are major defense mechanisms against viral infection. People with co-morbid conditions who are more prone to COVID-19-related deaths due to immune dysregulation are likely to benefit from consuming nutritional supplements that enhance the immune system. We recommend clinical studies to validate AFO-202 beta glucan in COVID-19 patients to prove its efficacy in overcoming a hyper-inflammation status, thus reducing the mortality, until a definite vaccine is made available.
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http://dx.doi.org/10.3389/fimmu.2020.01548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363949PMC
August 2020

Cross-Protection Induced by Encephalitis Vaccines against COVID-19 Might be a Reason for Relatively Lower Mortality Rate in Some Countries.

Arch Acad Emerg Med 2020 21;8(1):e54. Epub 2020 Apr 21.

Yamanashi University-Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi 409-3898, Japan.

COronaVIrus Disease 2019 (COVID-19) is an on-going pandemic attributed to a novel virus named SARS-CoV-2. Comparing the statistics of incidence and death rates between nations reveals that there is discrepancy amongst countries in these regards, even between countries that share borders. We herein present information from the literature indicating how cross-protection against COVID-19 conferred by the encephalitis vaccine could be the reason for lower fatality rate in the countries where immunization against encephalitis is widespread or included in national programs. This may pave the way for arriving at efficient prevention strategies as well as vaccine development.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212070PMC
April 2020

Articular chondrocytes from osteoarthritic knee joints of elderly, expanded in thermo-reversible gelation polymer (TGP), exhibiting higher UEA-1 expression in lectin microarray.

Regen Ther 2020 Jun 15;14:234-237. Epub 2020 May 15.

The Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), PB 1262, Chennai 600034, Tamil Nadu, India.

Autologous chondrocytes expanded, are used as tools of regenerative therapies for cartilage injuries. However, inability to maintain the hyaline phenotype both and post transplantation, remains one of the major hurdles for long term efficacy under clinical settings. We have reported earlier, hyaline phenotype maintenance of both human and rabbit chondrocytes for a long duration both when cultured conditions using a Thermo-reversible Gelation Polymer (TGP) scaffold-based methodology and post-transplantation animal model of cartilage damage. Having intrigued by such encouraging outcome, we in this study, analysed the similar TGP culture environment whether would be able to allow expansion of severe osteoarthritis affected cartilage tissue from elderly patients and evaluated the cells using lectin microarray characterization for pluripotency. Cartilage tissue were obtained from patients (n = 7; age: 60-85 years) undergoing total knee arthroplasty for severe osteoarthritis. Chondrocytes were isolated and cultured in two groups: i. conventional culture without scaffold (2D) and ii. using a TGP scaffold-based culture (3D) up to 18 weeks. In addition to earlier reported findings such as maintenance of hyaline phenotype having been confirmed in this study as well, surface glycoprotein analysis by lectin microarray demonstrated that the α1-2 Fuc recognition lectin (UEA-1) (marker reported in literature for pluripotent stem cells) was found to be more highly expressed in 3D culture compared to 2D culture and even increased over time in 3D culture. We have developed an environment where osteoarthritis affected chondrocytes from the elderly could be cultured up to 18 weeks using TGP scaffold which express pluripotent cell associated surface glycoproteins compared to the conventional methodology.
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http://dx.doi.org/10.1016/j.reth.2020.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229400PMC
June 2020

Cell-based immunotherapy in stage IIIA inflammatory breast cancer with declining innate immunity following successive chemotherapies: A case report.

Mol Clin Oncol 2017 Sep 19;7(3):493-497. Epub 2017 Jul 19.

The Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, Tamil Nadu 600034, India.

Cancer stem cells in breast cancer migrating to the bone marrow may cause future metastasis, particularly during periods of decreased immunity. Natural killer (NK) cells have a role in immune surveillance and are able to target cancer stem cells. The present study reported a case in which NK cell-based autologous immune enhancement therapy was used combined with conventional treatments in a patient with stage IIIA breast cancer, yielding >28 months of disease-free survival. However, there was a gradual decline in the in vitro expansion of NK cells with subsequent chemotherapeutic treatments. As this NK cell decline following chemotherapy may contribute to cancer cell immune evasion and future metastasis; modifying current cancer therapies in order to avoid potentially compromising the immune system may lead to improved treatment outcomes.
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http://dx.doi.org/10.3892/mco.2017.1333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582509PMC
September 2017

Natural killer cells as a promising tool to tackle cancer-A review of sources, methodologies, and potentials.

Int Rev Immunol 2017 07 4;36(4):220-232. Epub 2017 May 4.

a The Fujio-Eiji Academic Terrain (FEAT) , Nichi-In Centre for Regenerative Medicine (NCRM) , Chennai , Tamil Nadu , India.

Immune cell-based therapies are emerging as a promising tool to tackle malignancies, both solid tumors and selected hematological tumors. Vast experiences in literature have documented their safety and added survival benefits when such cell-based therapies are combined with the existing treatment options. Numerous methodologies of processing and in vitro expansion protocols of immune cells, such as the dendritic cells, natural killer (NK) cells, NKT cells, αβ T cells, so-called activated T lymphocytes, γδ T cells, cytotoxic T lymphocytes, and lymphokine-activated killer cells, have been reported for use in cell-based therapies. Among this handful of immune cells of significance, the NK cells stand apart from the rest for not only their direct cytotoxic ability against cancer cells but also their added advantage, which includes their capability of (i) action through both innate and adaptive immune mechanism, (ii) tackling viruses too, giving benefits in conditions where viral infections culminate in cancer, and (iii) destroying cancer stem cells, thereby preventing resistance to chemotherapy and radiotherapy. This review thoroughly analyses the sources of such NK cells, methods for expansion, and the future potentials of taking the in vitro expanded allogeneic NK cells with good cytotoxic ability as a drug for treating cancer and/or viral infection and even as a prophylactic tool for prevention of cancer after initial remission.
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http://dx.doi.org/10.1080/08830185.2017.1284209DOI Listing
July 2017

Transplantation of autologous chondrocytes expanded using Thermoreversible Gelation Polymer in a rabbit model of articular cartilage defect.

J Orthop 2017 Jun 3;14(2):223-225. Epub 2017 Feb 3.

The Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India; II Department of Surgery, Yamanashi University- School of Medicine, Chuo, Japan.

Graft failure due to de-differentiation of the chondrocytes during in vitro culture and after transplantation is a major hurdle in Autologous Chondrocyte Implantation (ACI). We, herein, report the transplantation of autologous chondrocytes expanded using a Thermo-reversible Gelation Polymer (TGP) in a rabbit model. A full thickness chondral defect was created in one of the knee joints in each of the six rabbits of the study and autologous chondrocytes expanded using TGP scaffold were transplanted after 10 weeks. H & E staining of the biopsy after 6 months revealed maintenance of articular cartilage phenotype.
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http://dx.doi.org/10.1016/j.jor.2017.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293721PMC
June 2017

Autologous immune enhancement therapy in a case of gall bladder cancer stage IV after surgical resection and chemotherapy yielding a stable non-progressive disease.

J Cancer Res Ther 2014 Jul-Sep;10(3):752-4

The Mary-Yoshio Translational Hexagon, Nichi-In Centre for Regenerative Medicine, Chennai, Tamil Nadu, India; Yamanashi University-School of Medicine, Chuo, Japan.

Advanced gall bladder cancer generally has a poor prognosis and also shows decreased response to conventional therapies like chemotherapy and radiotherapy. Though surgical resection is the most common approach followed, the 1-year survival rate is only 10%. Herein, we report the outcome of administration of autologous natural killer cell and activated T lymphocyte-based autologous immune enhancement therapy (AIET) in a case of gall bladder cancer stage IV which was progressing in spite of surgical resection and several sittings of chemotherapy. There were no adverse reactions after AIET. After three infusions of AIET, an improvement of the quality of life and general condition which is sustaining for more than 6 months and a substantial decrease in the CA 19-9 marker levels from 2938.22 U/mL before AIET to 511 U/mL, 5 months after AIET, in our experience make us recommend AIET along with other conventional treatments in similar cases.
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http://dx.doi.org/10.4103/0973-1482.136048DOI Listing
June 2015

Periodontal regeneration by autologous bone marrow mononuclear cells embedded in a novel thermo reversible gelation polymer.

J Stem Cells 2013 ;8(2):99-103

Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, Tamilnadu, India

Regeneration of bony defects caused by periodontal disease continues to be a challenge for clinicians. Application of stem cells from different tissue sources and scaffolds for regeneration have been reported in animal models but clinical studies with long term follow-ups are limited. Herein we report the three years follow-up of the application of autologous bone marrow mononuclear cells (BMMNCs) embedded in a thermo-reversible gelation polymer (TGP) for periodontal regeneration. A 23-year female patient with advanced periodontitis (class IV gingival recession, probing pocket depth (PPD) of 5 mm and 6 mm in relation to mandibular lateral and central incisors respectively, and clinical attachment level (CAL) of 13 mm) correlated with radiographic evidence of severe horizontal bone loss extending up to the apex of mandibular incisors was selected for the treatment. After debridement, the defect was implanted with BMMNCs impregnated in TGP. Then the clinical parameters and radiographic evaluation were made at periodic intervals of 6, 12, 24 and 36 months. At six months, significant improvement with the clinical parameters (PPD had reduced to 2 mm, clinical attachment level had improved by 6 mm) was observed. At 36 months, the radiograph revealed bone regeneration with improvement in vertical and horizontal bone height. Transplantation of BMMNCs in a novel TGP is safe and results in a relatively significant and stable clinical outcome in horizontal alveolar bony defects.
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http://dx.doi.org/jsc.2014.8.2.99DOI Listing
May 2014

The known-unknowns in spinal cord injury, with emphasis on cell-based therapies - a review with suggestive arenas for research.

Expert Opin Biol Ther 2014 May 24;14(5):617-34. Epub 2014 Mar 24.

Nichi-In Centre for Regenerative Medicine (NCRM), The Mary-Yoshio Translational Hexagon (MYTH) , PB 1262, Chennai - 600034, Tamil Nadu , India +91 44 24732186 ; ,

Introduction: In spite of extensive research, the progress toward a cure in spinal cord injury (SCI) is still elusive, which holds good for the cell- and stem cell-based therapies. We have critically analyzed seven known gray areas in SCI, indicating the specific arenas for research to improvise the outcome of cell-based therapies in SCI.

Areas Covered: The seven, specific known gray areas in SCI analyzed are: i) the gap between animal models and human victims; ii) uncertainty about the time, route and dosage of cells applied; iii) source of the most efficacious cells for therapy; iv) inability to address the vascular compromise during SCI; v) lack of non-invasive methodologies to track the transplanted cells; vi) need for scaffolds to retain the cells at the site of injury; and vii) physical and chemical stimuli that might be required for synapses formation yielding functional neurons.

Expert Opinion: Further research on scaffolds for retaining the transplanted cells at the lesion, chemical and physical stimuli that may help neurons become functional, a meta-analysis of timing of the cell therapy, mode of application and larger clinical studies are essential to improve the outcome.
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http://dx.doi.org/10.1517/14712598.2014.889676DOI Listing
May 2014

Age-old wisdom concerning cell-based therapies with added knowledge in the stem cell era: our perspectives.

Stem Cells Cloning 2013 4;6:13-8. Epub 2013 Apr 4.

Nichi-In Centre for Regenerative Medicine, Chennai, India ; Yamanashi University School of Medicine, Chuo, Japan.

Among the various strategies providing a cure for illness, cell-based therapies have caught the attention of the world with the advent of the "stem cell" era. Our inherent understanding indicates that stem cells have been in existence since the birth of multicellular organisms. However, the formal discovery of stem cells in the last century, followed by their intricate and extensive analysis, has led to clinical and translational efforts with the aim of using them in the treatment of conditions which don't have a definitive therapeutic strategy, has fueled our interest and expectations. Technological advances in our ability to study their cellular components in depth, along with surface markers and other finer constituents, that were unknown until last century, have improved our understanding, leading to several novel applications. This has created a need to establish guidelines, and in that process, there are expressed understandings and views which describe cell therapy along lines similar to that of biologic products, drugs, and devices. However, the age-old wisdom of using cells as tools for curing illness should not be misled by recent knowledge, to make cell therapy using highly complex stem cells equal to factory-synthesized and reproducible chemical compounds, drugs, or devices. This article analyses the differences between these two entities from various perspectives.
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http://dx.doi.org/10.2147/SCCAA.S41798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850297PMC
January 2014

Beneficial effects of black yeast derived 1-3, 1-6 Beta Glucan-Nichi Glucan in a dyslipidemic individual of Indian origin--a case report.

J Diet Suppl 2014 Mar 10;11(1):1-6. Epub 2014 Jan 10.

1The Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Nungambakkam, Chennai 600034, India.

Dyslipidemia is a major risk factor for the development of cardiovascular diseases and statins are the common drugs used to correct dyslipidemia. Herein, we report a case where the subject was a nondiabetic, dyslipidemia patient on medication with Rosuvastatin. After the intake of Rosuvastatin, his triglycerides decreased to a minimum of 220 mg/dL. In order to augment the action of Rosuvastatin, he was advised to take 1.5 mg of Nichi Glucan food supplement, which is a 1,3-1,6 Beta Glucan derived from the black yeast, Aureobasidium pullulans, daily for 2 months. At the end of 2 months, his triglyceride levels decreased from 523 mg/dL (at start of the study) to 175 mg/dL. His VLDL levels, which were 104.6 mg/dL at the start of the study decreased to 35 mg/dL and the HDL cholesterol levels increased from 27 to 38 mg/dL. This is a first of its kind report on the effect of the black yeast derived 1,3-1,6 Beta Glucans on dyslipidemia not associated with diabetes. Thus supplementation of Nichi Glucan, 1,3- 1,6 Beta Glucan derived from the black yeast along with the routine medications was beneficial to treat dyslipidemia and a larger trial is needed to confirm the effects.
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http://dx.doi.org/10.3109/19390211.2013.859211DOI Listing
March 2014

Successful transportation of human corneal endothelial tissues without cool preservation in varying Indian tropical climatic conditions and in vitro cell expansion using a novel polymer.

Indian J Ophthalmol 2014 Feb;62(2):130-5

The Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine, Chennai, India; II Department of Surgery, Yamanashi University - School of Medicine, Chuo, Japan, .

Background: Though the transplantation of human corneal endothelial tissue (CET) separated from cadaver cornea is in practice, its transportation has not been reported. We report the successful transportation of CET in varying Indian climatic conditions without cool preservation and the in vitro expansion of Human Corneal Endothelial Precursor Cells (HCEPCs) using a novel Thermo-reversible gelation polymer (TGP).

Materials And Methods: CET from cadaver corneas (n = 67), unsuitable for transplantation, were used. In phase I, CET was transported in Basal Culture Medium (Group I) and TGP (Group II) and in Phase II, in TGP cocktail alone, from three hospitals 250-2500 km away, to a central laboratory. The transportation time ranged from 6 h to 72 h and the outdoor temperature between 20°C and 41°C. On arrival, CET were processed, cells were expanded upto 30 days in basal culture medium (Group A) and TGP scaffold (Group B). Cell viability and morphology were documented and Reverse transcription polymerase chain reaction (RT-PCR) characterization undertaken.

Results: In Phase I, TGP yielded more viable cells (0.11 × 10(6) cells) than Group I (0.04 × 10(6) cells). In Phase II, the average cell count was 5.44 × 10(4) cells. During expansion, viability of HCEPCs spheres in TGP was maintained for a longer duration. The cells from both the groups tested positive for B-3 tubulin and negative for cytokeratins K3 and K12, thereby proving them to be HCEPCs.

Conclusion: TGP preserves the CET during transportation without cool preservation and supports in vitro expansion, with a higher yield of HCEPCs, similar to that reported in clinical studies.
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http://dx.doi.org/10.4103/0301-4738.116457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005225PMC
February 2014

Smallpox still haunts scientists: results of a questionnaire-based inquiry on the views of health care and life science experts and students on preserving the remaining variola virus stocks.

ScientificWorldJournal 2013 22;2013:672813. Epub 2013 Jul 22.

The Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai 600034, India.

The World Health Organization (WHO) declared eradication of the dreadful disease "smallpox" in 1980. Though the disease has died down, the causative virus "variola" has not, as it has been well preserved in two high security laboratories-one in USA and another in Russia. The debate on whether the remaining stocks of the smallpox virus should be destroyed or not is ongoing, and the World Health Assembly (WHA) in 2011 has decided to postpone the review on this debate to the 67th WHA in 2014. A short questionnaire-based inquiry was organized during a one-day stem cell meeting to explore the views of various health care and life science specialists especially students on this aspect. Among the 200 participants of the meeting, only 66 had answered the questionnaire. 60.6% of participants who responded to the questionnaire were for preserving the virus for future reference, while 36.4% of the participants were for destroying the virus considering the magnitude with which it killed millions. However, 3% of the respondents were not able to decide on any verdict. Therefore, this inquiry expresses the view that "what we cannot create, we do not have the right to destroy."
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http://dx.doi.org/10.1155/2013/672813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736420PMC
February 2014

In vitro culture and characterization of enteric neural precursor cells from human gut biopsy specimens using polymer scaffold.

Intractable Rare Dis Res 2013 Aug;2(3):98-102

The Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Nungambakkam, Chennai, India; ; Yamanashi University- School of Medicine, Chuo, Yamanashi, Japan;

In vitro expansion and characterization of neural precursor cells from human gut biopsy specimens with or without Hirschsprung's disease using a novel thermoreversible gelation polymer (TGP) is reported aiming at a possible future treatment. Gut biopsy samples were obtained from five patients undergoing gut resection for Hirschsprung's disease (n = 1) or gastrointestinal disorders (n = 4). Cells isolated from the smooth muscle layer and the myenteric plexus were cultured in two groups for 18 to 28 days; Group I: conventional culture as earlier reported and Group II: using TGP scaffold. Neurosphere like bodies (NLBs) were observed in the cultures between 8th to 12th day and H & E staining was positive for neural cells in both groups including aganglionic gut portion from the Hirschsprung's disease patient. Immunohistochemistry using S-100 and neuron specific enolase (NSE) was positive in both groups but the TGP group (Group II) showed more number of cells with intense cytoplasmic granular positivity for both NSE and S-100 compared to Group I. TGP supports the in vitro expansion of human gut derived neuronal cells with seemingly better quality NLBs. Animal Studies can be tried to validate their functional outcome by transplanting the NLBs with TGP scaffolds to see whether this can enhance the outcome of cell based therapies for Hirschsprung's disease.
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http://dx.doi.org/10.5582/irdr.2013.v2.3.98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204546PMC
August 2013

Cell Based Autologous Immune Enhancement Therapy (AIET) after Radiotherapy in a Locally Advanced Carcinoma of the Cervix.

Case Rep Oncol Med 2013 7;2013:903094. Epub 2013 Apr 7.

Chennai Meenakshi Multispeciality Hospital Limited, New No. 72, Old No. 148, Luz Church Road, Mylapore, Chennai 600 004, India ; Dr. Kamakshi Memorial Hospital, 1 Radial Road, Pallikaranai, Chennai 600100, India.

Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET) for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life.
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http://dx.doi.org/10.1155/2013/903094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3638504PMC
July 2013

Potential effects of nichi glucan as a food supplement for diabetes mellitus and hyperlipidemia: preliminary findings from the study on three patients from India.

Case Rep Med 2012 10;2012:895370. Epub 2012 Dec 10.

Division of Translational Medicine, Nichi-In Centre for Regenerative Medicine (NCRM), PB 2278, Tamil Nadu, Chennai 600094, India.

Beta Glucan food supplements have been reported to be of benefit in diabetes and hyperlipidemia. We report a pilot study of the effects of Nichi Glucan, 1, 3-1, 6 Beta Glucan food supplement, in lowering the blood glucose and lipid levels in three patients with noninsulin-dependent diabetes mellitus (NIDDM) from India. These patients had increased blood glucose and lipid levels inspite of routine antidiabetic and lipid level lowering medications. Each of the participants took 1.5 g of Nichi Glucan per day with food for two months along with their routine medications. The relevant parameters to assess glycemic status and lipid levels were calculated at the baseline and at the end of two months. After two months of continuous consumption, in one patient, the HbA1c decreased from 9.1% to 7.8%, and the glycemic target of HbA1c <6.5% laid down by the International Diabetes Federation was reached in two patients. Lipid levels also decreased significantly. Based on our findings, Nichi Glucan food supplement can be considered along with routine medications in patients with Type II diabetes with hyperlipidemia. Further studies are needed to validate the results.
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http://dx.doi.org/10.1155/2012/895370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529881PMC
January 2013

A comparative analysis of in vitro expansion of natural killer cells of a patient with autoimmune haemolytic anaemia and ovarian cancer with patients with other solid tumours.

Oncol Lett 2012 Feb 29;3(2):435-440. Epub 2011 Nov 29.

Nichi-In Centre for Regenerative Medicine, Chennai, India.

The functional profile of natural killer (NK) cells has been reported to be lower in auto-immune haemolytic anaemia (AIHA). In this study, we report a comparative analysis of peripheral blood mononuclear cells (PBMNCs) and the in vitro expansion of NK cells in a patient with AIHA and cancer, with that of other cancer patients without AIHA. PBMNCs and in vitro NK-cell expansion of a 64-year old female patient with ovarian cancer and AIHA was compared with that of four other patients with cancer without AIHA who underwent autologous immune enhancement therapy (AIET). The NK cells were cultured using autologous plasma without feeder layers. The quantities of PBMNCs, NK cells and CD3-CD56+ cells were compared. The average quantity of PBMNCs per ml in Cases I to V were 10.71, 39.2, 49.26, 65.16 and 49.33×10(4), respectively, and the average maximum count of NK cells was 3.9, 1730.03, 1824.16, 1058.61 and 761×10(6), respectively. The average percentage of CD3-CD56+ cells in Cases I to V following in vitro expansion was 1.2, 65.7, 28.63, 65.9 and 40%, respectively. In the present study, probably the first in the literature, the in vitro expansion of NK cells was found to be significantly lower in the AIHA patient. Previously, only a lower NK-cell functional profile was reported. Further studies are required to establish the association between AIHA and NK-cell profile and in vitro expansion, and to find common antibodies between red blood cells (RBCs) and NK cells.
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http://dx.doi.org/10.3892/ol.2011.498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362377PMC
February 2012

Autologous immune enhancement therapy in recurrent ovarian cancer with metastases: a case report.

Case Rep Oncol 2012 Jan 16;5(1):114-8. Epub 2012 Mar 16.

Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India.

Current therapeutic modalities for ovarian cancer such as chemotherapy, radiotherapy and surgery have been reported to yield only marginal success in improving survival rates of patients and have associated adverse effects. We report here a case of recurrent stage IV ovarian cancer, treated with cell-based autologous immune enhancement therapy (AIET) along with chemotherapy and followed up for 18 months. A 54-year-old female was diagnosed with a recurrence of ovarian carcinoma 1 year after initial surgical removal followed by chemotherapy for stage IIIC ovarian carcinoma. When diagnosed in 2010 with recurrence, she had liver and spleen metastases with a CA-125 level of 243 U/ml and a stage IV clinical status. Six infusions of AIET using autologous in vitro expanded and activated natural killer (NK) cells (CD3-CD56+) and activated T lymphocytes (CD3+CD56+) were administered in combination with 6 cycles of chemotherapy with carboplatin and doxorubicin. Following this treatment, CA-125 decreased to 4.7 U/ml along with regression of the metastatic lesions and an improved quality of life. No adverse reactions were reported after the AIET transfusions. Eighteen months of follow-up revealed a static nonprogressive disease. Combining AIET with chemotherapy and other conventional treatments has been found to be effective in our experience, as reported earlier, even in patients with advanced ovarian cancer, and we recommend this strategy be considered in treating similar cases.
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http://dx.doi.org/10.1159/000337319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364094PMC
January 2012