Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model

Jaianand Kannaiyan; Pavankumar Shukla; Firdosh Mahuvawalla

doi:doi:10.11648/j.rs.20220702.12

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Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model

Jaianand Kannaiyan, Pavankumar Shukla, Firdosh Mahuvawalla

Published in Rehabilitation Science (Volume 7, Issue 2)

Received: 16 March 2022 Accepted: 11 April 2022 Published: 12 May 2022

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Abstract

In-vitro and in-vivo investigations using ex vivo-expanded human Wharton’s jelly-derived mesenchymal stromal cells (WJMSCs) isolated from single donors has shown therapeutic advantages. Clinical grade expansion, safety, and acute toxicity of Wharton’s jelly-derived mesenchymal stromal cells isolated from five healthy donors were evaluated in Wistar Albino Rats via intravenous and subcutaneous routes in this study. The expression of several cell surface markers, differentiation capacity, and immunomodulatory activities of the isolated WJMSCs were all evaluated. In a series of preclinical investigations, the clinical grade expanded cells were given to rodents by intravenous and subcutaneous methods to examine their in-vivo safety, overall toxicity, and tumorigenic potential. We confirmed that WJ cells exhibit morphological and phenotypic features that are comparable to MSCs. In rats, the study found no mortality, aberrant clinical symptoms, or significant pathological alterations at varied dosages administered intravenously or subcutaneously. Furthermore, rats tolerated repeated treatment of WJMSCs well, with no evidence of prenatal harm in the same animal species. The WJMSCs were shown to be non-toxic, non-teratogenic, and non-tumorigenic in Wistar Albino Rats. More research is needed to see if it can be safely supplied to human patients.

Published in	Rehabilitation Science (Volume 7, Issue 2)
DOI	10.11648/j.rs.20220702.12
Page(s)	20-28
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2022. Published by Science Publishing Group

Keywords

Wharton's Jelly, Umbilical Cord Mesenchymal Stromal Cells, Intravenous, Subcutaneous, Safety, Toxicity

References

[1]	Singer NG, Caplan AI. “Mesenchymal stem cells: mechanisms of inflammation,” Annu Rev Pathol. 2011; 6: 457-78.
[2]	Ding DC, Shyu WC, Lin SZ. “Mesenchymal stem cells. Cell Transplant,” 2011; 20 (1): 5-14.
[3]	Hassan MNFB, Yazid MD, Yunus MHM, Chowdhury SR, Lokanathan Y, Idrus RBH, Ng AMH, Law JX. “Large-Scale Expansion of Human Mesenchymal Stem Cells,” Stem Cells Int. 2020; 15; 2020: 9529465.
[4]	Lukomska B, Stanaszek L, Zuba-Surma E, Legosz P, Sarzynska S, Drela K. “Challenges and Controversies in Human Mesenchymal Stem Cell Therapy. Stem Cells,” Int. 2019; 9; 2019: 9628536.
[5]	Pal R, Hanwate M, Jan M, Totey S. “Phenotypic and functional comparison of optimum culture conditions for upscaling of bone marrow-derived mesenchymal stem cells,” J Tissue Eng Regen Med. 2009; 3 (3): 163-74.
[6]	Peng L, Jia Z, Yin X, Zhang X, Liu Y, Chen P, Ma K, Zhou C. “Comparative analysis of mesenchymal stem cells from bone marrow, cartilage, and adipose tissue,” Stem Cells Dev. 2008; 17 (4): 761-73.
[7]	Hu Y, Liang J, Cui H, Wang X, Rong H, Shao B, Cui H. “Wharton's jelly mesenchymal stem cells differentiate into retinal progenitor cells,” Neural Regen Res. 2013; 5; 8 (19): 1783-92.
[8]	Wang Y, Han ZB, Song YP, Han ZC. “Safety of mesenchymal stem cells for clinical application,” Stem Cells Int. 2012; 2012: 652034.
[9]	Thirumala S, Goebel WS, Woods EJ. “Clinical grade adult stem cell banking. Organogenesis,” 2009; 5 (3): 143-54.
[10]	Cooper K, Viswanathan C. “Establishment of a mesenchymal stem cell bank,” Stem Cells Int. 2011; DOI: 10.4061/2011/905621s.
[11]	Viswanathan C, Davidson Y, Cooper K, Tipnis S, Pujari G, Kurian VM. “Tansplantation of autologous bone marrow derived mesenchymal stem cells trans-epicardially in patients undergoing coronary bypass surgery,” Indian Heart J. 2010; 62 (1): 43-8.
[12]	Amer MH, Rose FRAJ, Shakesheff KM, Modo M, White LJ. “Translational considerations in injectable cell-based therapeutics for neurological applications: concepts, progress and challenges,” NPJ Regen Med. 2017; 10; 2: 23.
[13]	Huang XP, Sun Z, Miyagi Y, McDonald Kinkaid H, Zhang L, Weisel RD, Li RK. “Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair,” Circulation. 2010; 7; 122 (23): 2419-29.
[14]	Musiał-Wysocka A, Kot M, Majka M. “The Pros and Cons of Mesenchymal Stem Cell-Based Therapies. Cell Transplant,” 2019; 28 (7): 801-812.
[15]	Jaianand K, Balaji P. “Clinical Prospects of Scale-Up foetal Wharton's Jelly-Derived Multipotent Stromal Cells to fulfil the Therapeutic Demands,” Int J Pharm. Bio. Sci. 2015; 6 (4): B882-B894.
[16]	Jaianand K, Balaji P. “Isolation, Characterization and Scale-Up of Foetal Amniotic Membrane-Derived Multipotent Stromal Cells for Therapeutic Applications,” Int J Pharm. Bio. Sci. 2015; 6 (2): 376-385.
[17]	Dominici M, Le BK, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E. “Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement,” Cytotherapy. 2006; 8 (4): 315-317.
[18]	Williams AR and Hare JM. “Mesenchymal stem cells: Biology, pathophysiology, translational findings and therapeutic implications for cardiac diseases,” Circulation Research, 2011; 108 (8): 923-940.
[19]	Devang MP, Jainy S and Anand S. “Therapeutic potential of Mesenchymal Stem Cells in Regenerative Medicines,” Stem cell international. 2013; 2013: 496218: 15.
[20]	Nekanti U, Mohanty L, Venugopal P, Balasubramanian S, Totey S and Ta. M. “Optimization and scale up of Wharton’s jelly derived mesenchymal stem cells for clinical applications,” Stem cell research. 2010; 5 (3): 244-254.
[21]	Young Bang O, Jin SL, Hyu Lee and Gwang Lee. “Autologous mesenchymal stem cell transplantation in stroke patients,” Annals of Neurology. 2005; 57: 874–882.
[22]	Pal R, Venkataramana NK., Bansal A, Balaraju S, Jan M, Chandra R, Dixit A, Rauthan A, Murgod U and Totey S. “Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study,” Cytotherapy. 2009; 11 (7): 897-911.
[23]	Martino G, Franklin RJ, VanEvercooren AB and Kerr DA. “Stem cells in multiple sclerosis (STEMS) consensus group. Stem cell transplantation in multiple sclerosis: current status and future prospects,” Nature Reviews Neurology. 2010; 6 (5): 247–255.
[24]	Freedman MS, Bar-Or A, Atkins HL. Karussis D, Frassoni F, Lazarus H, Scolding N, Slavin S, Le Blanc K, Uccelli A; MSCT Study Group. “The therapeutic potential of mesenchymal stem cell transplantation as a treatment for multiple sclerosis: consensus report of the International MSCT Study Group,” Multiple Sclerosis. 2010; 16 (4): 503–510.
[25]	Wang D, Akiyama K, Zhang H., Yamaza T, Li X, Feng X, Wang H, Hua B, Liu B, Xu H, Chen W, Shi S and Sun L. “Double allogenic mesenchymal stem cells transplantations could not enhance therapeutic effect compared with single transplantation in systemic lupus erythematosus,” Clinical and Development Immunology. 2012; 2012: 273291.
[26]	Reinders ME, de Fijter JW, Roelofs H, Bajema IM, de Vries DK, Schaapherder AF, Claas FH, van Miert PP, Roelen DL, van Kooten C, Fibbe WE and Rabelink TJ. “Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study,” Stem Cells Translational Medicine. 2013; 2 (2), 107-11.
[27]	Kim SJ, Moon GJ, Chang WH., Kim YH and O. Y. Bang. “Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial,” Stem cell Application Researches and Trials In Neurology. 2013; 14 (1): 317.

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APA Style

Jaianand Kannaiyan, Pavankumar Shukla, Firdosh Mahuvawalla. (2022). Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model. Rehabilitation Science, 7(2), 20-28. https://doi.org/10.11648/j.rs.20220702.12

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ACS Style

Jaianand Kannaiyan; Pavankumar Shukla; Firdosh Mahuvawalla. Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model. Rehabil. Sci. 2022, 7(2), 20-28. doi: 10.11648/j.rs.20220702.12

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AMA Style

Jaianand Kannaiyan, Pavankumar Shukla, Firdosh Mahuvawalla. Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model. Rehabil Sci. 2022;7(2):20-28. doi: 10.11648/j.rs.20220702.12

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@article{10.11648/j.rs.20220702.12,
  author = {Jaianand Kannaiyan and Pavankumar Shukla and Firdosh Mahuvawalla},
  title = {Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model},
  journal = {Rehabilitation Science},
  volume = {7},
  number = {2},
  pages = {20-28},
  doi = {10.11648/j.rs.20220702.12},
  url = {https://doi.org/10.11648/j.rs.20220702.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.rs.20220702.12},
  abstract = {In-vitro and in-vivo investigations using ex vivo-expanded human Wharton’s jelly-derived mesenchymal stromal cells (WJMSCs) isolated from single donors has shown therapeutic advantages. Clinical grade expansion, safety, and acute toxicity of Wharton’s jelly-derived mesenchymal stromal cells isolated from five healthy donors were evaluated in Wistar Albino Rats via intravenous and subcutaneous routes in this study. The expression of several cell surface markers, differentiation capacity, and immunomodulatory activities of the isolated WJMSCs were all evaluated. In a series of preclinical investigations, the clinical grade expanded cells were given to rodents by intravenous and subcutaneous methods to examine their in-vivo safety, overall toxicity, and tumorigenic potential. We confirmed that WJ cells exhibit morphological and phenotypic features that are comparable to MSCs. In rats, the study found no mortality, aberrant clinical symptoms, or significant pathological alterations at varied dosages administered intravenously or subcutaneously. Furthermore, rats tolerated repeated treatment of WJMSCs well, with no evidence of prenatal harm in the same animal species. The WJMSCs were shown to be non-toxic, non-teratogenic, and non-tumorigenic in Wistar Albino Rats. More research is needed to see if it can be safely supplied to human patients.},
 year = {2022}
}

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TY  - JOUR
T1  - Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model
AU  - Jaianand Kannaiyan
AU  - Pavankumar Shukla
AU  - Firdosh Mahuvawalla
Y1  - 2022/05/12
PY  - 2022
N1  - https://doi.org/10.11648/j.rs.20220702.12
DO  - 10.11648/j.rs.20220702.12
T2  - Rehabilitation Science
JF  - Rehabilitation Science
JO  - Rehabilitation Science
SP  - 20
EP  - 28
PB  - Science Publishing Group
SN  - 2637-594X
UR  - https://doi.org/10.11648/j.rs.20220702.12
AB  - In-vitro and in-vivo investigations using ex vivo-expanded human Wharton’s jelly-derived mesenchymal stromal cells (WJMSCs) isolated from single donors has shown therapeutic advantages. Clinical grade expansion, safety, and acute toxicity of Wharton’s jelly-derived mesenchymal stromal cells isolated from five healthy donors were evaluated in Wistar Albino Rats via intravenous and subcutaneous routes in this study. The expression of several cell surface markers, differentiation capacity, and immunomodulatory activities of the isolated WJMSCs were all evaluated. In a series of preclinical investigations, the clinical grade expanded cells were given to rodents by intravenous and subcutaneous methods to examine their in-vivo safety, overall toxicity, and tumorigenic potential. We confirmed that WJ cells exhibit morphological and phenotypic features that are comparable to MSCs. In rats, the study found no mortality, aberrant clinical symptoms, or significant pathological alterations at varied dosages administered intravenously or subcutaneously. Furthermore, rats tolerated repeated treatment of WJMSCs well, with no evidence of prenatal harm in the same animal species. The WJMSCs were shown to be non-toxic, non-teratogenic, and non-tumorigenic in Wistar Albino Rats. More research is needed to see if it can be safely supplied to human patients.
VL  - 7
IS  - 2
ER  -

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Author Information

Jaianand Kannaiyan

Research and Development, Cell Cure Therapeutics, Coimbatore, India
Pavankumar Shukla

Regeneracion Corporation, Vigan City, Philippines
Firdosh Mahuvawalla

Regeneracion Corporation, Vigan City, Philippines

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APA Style

Jaianand Kannaiyan, Pavankumar Shukla, Firdosh Mahuvawalla. (2022). Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model. Rehabilitation Science, 7(2), 20-28. https://doi.org/10.11648/j.rs.20220702.12

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ACS Style

Jaianand Kannaiyan; Pavankumar Shukla; Firdosh Mahuvawalla. Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model. Rehabil. Sci. 2022, 7(2), 20-28. doi: 10.11648/j.rs.20220702.12

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AMA Style

Jaianand Kannaiyan, Pavankumar Shukla, Firdosh Mahuvawalla. Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model. Rehabil Sci. 2022;7(2):20-28. doi: 10.11648/j.rs.20220702.12

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@article{10.11648/j.rs.20220702.12,
  author = {Jaianand Kannaiyan and Pavankumar Shukla and Firdosh Mahuvawalla},
  title = {Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model},
  journal = {Rehabilitation Science},
  volume = {7},
  number = {2},
  pages = {20-28},
  doi = {10.11648/j.rs.20220702.12},
  url = {https://doi.org/10.11648/j.rs.20220702.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.rs.20220702.12},
  abstract = {In-vitro and in-vivo investigations using ex vivo-expanded human Wharton’s jelly-derived mesenchymal stromal cells (WJMSCs) isolated from single donors has shown therapeutic advantages. Clinical grade expansion, safety, and acute toxicity of Wharton’s jelly-derived mesenchymal stromal cells isolated from five healthy donors were evaluated in Wistar Albino Rats via intravenous and subcutaneous routes in this study. The expression of several cell surface markers, differentiation capacity, and immunomodulatory activities of the isolated WJMSCs were all evaluated. In a series of preclinical investigations, the clinical grade expanded cells were given to rodents by intravenous and subcutaneous methods to examine their in-vivo safety, overall toxicity, and tumorigenic potential. We confirmed that WJ cells exhibit morphological and phenotypic features that are comparable to MSCs. In rats, the study found no mortality, aberrant clinical symptoms, or significant pathological alterations at varied dosages administered intravenously or subcutaneously. Furthermore, rats tolerated repeated treatment of WJMSCs well, with no evidence of prenatal harm in the same animal species. The WJMSCs were shown to be non-toxic, non-teratogenic, and non-tumorigenic in Wistar Albino Rats. More research is needed to see if it can be safely supplied to human patients.},
 year = {2022}
}

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TY  - JOUR
T1  - Acute Toxicity Evaluation and Safety Study of Allogeneic Wharton’s Jelly-Derived Mesenchymal Stromal Cells Therapy in the Animal Model
AU  - Jaianand Kannaiyan
AU  - Pavankumar Shukla
AU  - Firdosh Mahuvawalla
Y1  - 2022/05/12
PY  - 2022
N1  - https://doi.org/10.11648/j.rs.20220702.12
DO  - 10.11648/j.rs.20220702.12
T2  - Rehabilitation Science
JF  - Rehabilitation Science
JO  - Rehabilitation Science
SP  - 20
EP  - 28
PB  - Science Publishing Group
SN  - 2637-594X
UR  - https://doi.org/10.11648/j.rs.20220702.12
AB  - In-vitro and in-vivo investigations using ex vivo-expanded human Wharton’s jelly-derived mesenchymal stromal cells (WJMSCs) isolated from single donors has shown therapeutic advantages. Clinical grade expansion, safety, and acute toxicity of Wharton’s jelly-derived mesenchymal stromal cells isolated from five healthy donors were evaluated in Wistar Albino Rats via intravenous and subcutaneous routes in this study. The expression of several cell surface markers, differentiation capacity, and immunomodulatory activities of the isolated WJMSCs were all evaluated. In a series of preclinical investigations, the clinical grade expanded cells were given to rodents by intravenous and subcutaneous methods to examine their in-vivo safety, overall toxicity, and tumorigenic potential. We confirmed that WJ cells exhibit morphological and phenotypic features that are comparable to MSCs. In rats, the study found no mortality, aberrant clinical symptoms, or significant pathological alterations at varied dosages administered intravenously or subcutaneously. Furthermore, rats tolerated repeated treatment of WJMSCs well, with no evidence of prenatal harm in the same animal species. The WJMSCs were shown to be non-toxic, non-teratogenic, and non-tumorigenic in Wistar Albino Rats. More research is needed to see if it can be safely supplied to human patients.
VL  - 7
IS  - 2
ER  -

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