Stem Cell Reviews and Reports

, Volume 13, Issue 6, pp 713–724 | Cite as

Pluripotent Stem Cells in Adult Tissues: Struggling To Be Acknowledged Over Two Decades

Article

Abstract

Stem cells have fascinated scientists for a long time and huge research efforts have been put into them as they have the potential to regenerate diseased organs. Besides embryonic stem cells (ES) and induced pluripotent stem cells (iPS), it has been postulated that pluripotent stem cells (PSCs) may also exist in various adult tissues. They are thought to be more primitive than the adult stem cells (ASCs), serve as a backup pool to give rise to ASCs and thus play a crucial role in maintaining life-long homeostasis. These PSCs could also be the embryonic stem cells in adult tissues that were proposed to initiate cancers according to the Embryonic Rest Hypothesis put forth in the nineteenth century. However, the very presence of PSCs in adult tissues is mired with controversies. This article is a sincere attempt to review research carried out by various investigators over the last two decades and various attempts to demonstrate their presence in adult tissues. Such adult PSCs could be the ideal stem cell candidates to bring about endogenous regeneration compared to ES/iPS cells grown in Petri dish and also score better over ASCs which in fact are tissue committed progenitors with limited regenerative potential that differentiate from the PSCs. PSCs in adult tissues have remained elusive until now as they possibly get unknowingly discarded due to their small size and inability to pellet at 1000–1200 rpm (250 g). They will likely prove to be a game changer in the field of stem cells biology, for regenerative medicine and for our understanding of cancer initiation.

Keywords

Pluripotent stem cells VSELs ES cells iPS cells MAPCs STAP cells MUSE cells Spore-like cells 

Notes

Acknowledgements

Significant contributions made by my students on VSELs research are sincerely acknowledged. Also author acknowledges the contributions of all other colleagues working on PSCs in adult tissues that are directly relevant but may not have been cited.

Compliance with Ethical Standards

Conflict of interest

Author declares no conflict of interest.

References

  1. 1.
    Tapia, N., & Schöler, H.R. (2016). Molecular obstacles to clinical translation of iPSCs. Cell Stem Cell, 19(3), 298–309.PubMedCrossRefGoogle Scholar
  2. 2.
    Yoshihara, M., Hayashizaki, Y., & Murakawa, Y. (2016). Genomic instability of iPSCs: challenges towards their clinical applications. Stem Cell Reviews, 13(1), 7–16.PubMedCentralCrossRefGoogle Scholar
  3. 3.
    Kang, E., Wang, X., Tippner-Hedges, R., Ma, H., Folmes, C. D., Gutierrez, N. M., et al. (2016). Age-related accumulation of somatic mitochondrial DNA mutations in adult-derived human iPSCs. Cell Stem Cell, 18(5), 625–636.PubMedCrossRefGoogle Scholar
  4. 4.
    Yui, Y. (2016). Questions surrounding iPS cells in Japan. International Journal of Stem Cells, 9(1), 1–2.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Holden, C., & Vogel, G. (2002). Plasticity: time for a reappraisal? Science, 296, 2126–2129.PubMedCrossRefGoogle Scholar
  6. 6.
    Ogawa, M., LaRue, A.C., & Mehrotra, M. (2013) Hematopoietic stem cells are pluripotent and not just “hematopoietic”. Blood Cells Molecules & Diseases, 51(1),3–8.CrossRefGoogle Scholar
  7. 7.
    Ogawa, M., LaRue, A. C., & Mehrotra, M. (2015). Plasticity of hematopoietic stem cells. Best Practice & Research. Clinical Haematology, 28(2–3), 73–80.CrossRefGoogle Scholar
  8. 8.
    Bhartiya, D. (2015). Stem cells, progenitors & regenerative medicine: a retrospection. The Indian Journal of Medical Research, 141(2), 154–161.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Kuriyan, A. E., Albini, T. A., Townsend, J. H., Rodriguez, M., Pandya, H. K., Leonard, R. E., et al. (2017). Vision loss after intravitreal injection of autologous “stem cells” for AMD. The New England Journal of Medicine, 376(11), 1047–1053.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Marks, P. W., Witten, C. M., & Califf, R. M. (2017). Clarifying stem-cell therapy’s benefits and risks. The New England Journal of Medicine, 376(11), 1007–1009.PubMedCrossRefGoogle Scholar
  11. 11.
    Gao, L., Thilakavathy, K., & Nordin, N. (2013). A plethora of human pluripotent stem cells. Cell Biology International, 37(9), 875–887.PubMedCrossRefGoogle Scholar
  12. 12.
    Sharkis, S. J., Collector, M. I., Barber, J. P., Vala, M. S., & Jones, R. J. (1997). Phenotypic and functional characterization of the hematopoietic stem cell. Stem Cells, 15(Suppl 1), 41–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Randall, T. D., & Weissman, I. L. (1998). Characterization of a population of cells in the bone marrow that phenotypically mimics hematopoietic stem cells: resting stem cells or mystery population? Stem Cells, 16(1), 38–48.PubMedCrossRefGoogle Scholar
  14. 14.
    Krause, D. S., Theise, N. D., Collector, M. I., Henegariu, O., Hwang, S., Gardner, R., et al. (2004). Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell, 105(3), 369–377.CrossRefGoogle Scholar
  15. 15.
    Kassmer, S. H., & Krause, D. S. (2013). Very small embryonic-like cells: biology and function of these potential endogenous pluripotent stem cells in adult tissues. Molecular Reproduction and Development, 80(8), 677–690.PubMedCrossRefGoogle Scholar
  16. 16.
    Suszynska, M., Pedziwiatr, D., Kucia, J. M., Ratajczak, Z. M., & Ratajczak, J. (2015). The bone marrow “mystery population” of stem cells 20 years later—a puzzle solved? Blood, 126, 2392.CrossRefGoogle Scholar
  17. 17.
    Vacanti, M. P., Roy, A., Cortiella, J., Bonassar, L., & Vacanti, C. A. (2001). Identification and initial characterization of spore-like cells in adult mammals. Journal of Cellular Biochemistry, 80(3), 455–460.PubMedCrossRefGoogle Scholar
  18. 18.
    Cortiella, J., Nichols, J. E., Kojima, K., Bonassar, L. J., Dargon, P., Roy, A. K., et al. (2006). Tissue-engineered lung: an in vivo and in vitro comparison of polyglycolic acid and pluronic F-127 hydrogel/ somatic lung progenitor cell constructs to support tissue growth. Tissue Engineering, 12(5), 1213–1225.PubMedCrossRefGoogle Scholar
  19. 19.
    Obokata, H., Kojima, K., Westerman, K., Yamato, M., Okano, T., Tsuneda, S., et al. (2011). The potential of stem cells in adult tissues representative of the three germ layers. Tissue Engineering Part A, 17(5–6), 607–615.PubMedCrossRefGoogle Scholar
  20. 20.
    Obokata, H., Wakayama, T., Sasai, Y., Kojima, K., Vacanti, M. P., Niwa, H., et al. (2014). Retraction: stimulus-triggered fate conversion of somatic cells into pluripotency. Nature, 511(7507), 112. RETRACTED.Google Scholar
  21. 21.
    Obokata, H., Sasai, Y., Niwa, H., Kadota, M., Andrabi, M., Takata, N., et al. (2014). Retraction: bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature, 511(7507), 112. RETRACTED.Google Scholar
  22. 22.
    Niwa, H. (2016). Investigation of the cellular reprogramming phenomenon referred to as stimulus-triggered acquisition of pluripotency (STAP). Science Reporter, 6, 28003.CrossRefGoogle Scholar
  23. 23.
    Aizawa, S. (2016). Results of an attempt to reproduce the STAP phenomenon. Version 2. F1000Res, 5:1056. doi: 10.12688/f1000research.8731.2.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    De Los Angeles, A., Ferrari, F., Fujiwara, Y., Mathieu, R., Lee, S., Lee, S., et al. (2015). Failure to replicate the STAP cell phenomenon. Nature, 525(7570), E6–E9.PubMedCrossRefGoogle Scholar
  25. 25.
    Tang, M. K., Lo, L. M., Shi, W. T., Yao, Y., Lee, H. S., & Lee, K. K. (2014). Transient acid treatment cannot induce neonatal somatic cells to become pluripotent stem cells. F1000Res, 3, 102. doi: 10.12688/f1000research.4092.1.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Bhartiya, D., Shaikh, A., Anand, S., Patel, H., Kapoor, S., Sriraman, K., et al. (2016). Endogenous, very small embryonic-like stem cells: critical review, therapeutic potential and a look ahead. Human Reproduction Update, 23(1), 41–76.PubMedCrossRefGoogle Scholar
  27. 27.
    Reyes, M., & Verfaillie, C. M. (2001). Characterization of multipotent adult progenitor cells, a subpopulation of mesenchymal stem cells. Annals of the New York Academy of Sciences, 938, 231–233. discussion 233-5.PubMedCrossRefGoogle Scholar
  28. 28.
    Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418(6893), 41–49.PubMedCrossRefGoogle Scholar
  29. 29.
    Serafini, M., Dylla, S. J., Oki, M., Heremans, Y., Tolar, J., Jiang, Y., et al. (2007). Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells. The Journal of Experimental Medicine, 204(1), 129–139.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Check, E. (2007). Stem-cell paper corrected. Nature, 447(7146):763.PubMedCrossRefGoogle Scholar
  31. 31.
    Plessers, J., Dekimpe, E., Van Woensel, M., Roobrouck, V. D., Bullens, D. M., Pinxteren, J., et al. (2016). Clinical-grade human multipotent adult progenitor cells block CD8 + cytotoxic T lymphocytes. Stem Cells Translational Medicine, 5(12), 1607–1619.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Kanatsu-Shinohara, M., Inoue, K., Lee, J., Yoshimoto, M., Ogonuki, N., Miki, H., et al. (2004). Generation of pluripotent stem cells from neonatal mouse testis. Cell, 119(7), 1001–1012.PubMedCrossRefGoogle Scholar
  33. 33.
    Guan, K., Nayernia, K., Maier, L. S., Wagner, S., Dressel, R., Lee, J. H., et al. (2006). Pluripotency of spermatogonial stem cells from adult mouse testis. Nature, 440(7088), 1199–1203.PubMedCrossRefGoogle Scholar
  34. 34.
    Conrad, S., Renninger, M., Hennenlotter, J., Wiesner, T., Just, L., Bonin, M., et al. (2008). Generation of pluripotent stem cells from adult human testis. Nature, 456(7220), 344–349. RETRACTED.PubMedCrossRefGoogle Scholar
  35. 35.
    Ko, K., Araúzo-Bravo, M. J., Tapia, N., Kim, J., Lin, Q., & Bernemann, C. (2010). Human adult germline stem cells in question. Nature, 24(7301), 465.Google Scholar
  36. 36.
    Chikhovskaya, J. V., van Daalen, S. K., Korver, C. M., Repping, S., & van Pelt, A. M. (2014). Mesenchymal origin of multipotent human testis-derived stem cells in human testicular cell cultures. Molecular Human Reproduction, 20(2), 155–167.PubMedCrossRefGoogle Scholar
  37. 37.
    Kanatsu-Shinohara, M., Morimoto, H., & Shinohara, T. (2016). Enrichment of mouse spermatogonial stem cells by the stem cell dye CDy1. Biology of Reproduction, 94(1), 13.PubMedCrossRefGoogle Scholar
  38. 38.
    Sadeghian-Nodoushan, F., Aflatoonian, R., Borzouie, Z., Akyash, F., Fesahat, F., Soleimani, M., et al. (2016). Pluripotency and differentiation of cells from human testicular sperm extraction: an investigation of cell stemness. Molecular Reproduction and Development, 83(4), 312–323.PubMedCrossRefGoogle Scholar
  39. 39.
    Bhartiya, D., Kasiviswananthan, S., & Shaikh, A. (2012). Cellular origin of testis-derived pluripotent stem cells: a case for very small embryonic-like stem cells. Stem Cells and Development, 21(5), 670–674.PubMedCrossRefGoogle Scholar
  40. 40.
    Kurkure, P., Prasad, M., Dhamankar, V., & Bakshi, G. (2015). Very small embryonic-like stem cells (VSELs) detected in azoospermic testicular biopsies of adult survivors of childhood cancer. Reproductive Biology and Endocrinology: RB&E. doi: 10.1186/s12958-015-0121-1.Google Scholar
  41. 41.
    Patel, H., & Bhartiya, D. (2016). Testicular stem cells express follicle-stimulating hormone receptors and are directly modulated by FSH. Reproductive Sciences, 23(11), 1493–1508.PubMedCrossRefGoogle Scholar
  42. 42.
    Kucia, M., Reca, R., Campbell, F. R., Zuba-Surma, E., Majka, M., Ratajczak, J., et al. (2006). A population of very small embryonic-like (VSEL) CXCR4 (+) SSEA-1(+) Oct-4 + stem cells identified in adult bone marrow. Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U. K., 20, 857–869.CrossRefGoogle Scholar
  43. 43.
    Ratajczak, M. Z. (2017). Why are hematopoietic stem cells so ‘sexy’? On a search for developmental explanation. Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U. K. doi: 10.1038/leu.2017.148.Google Scholar
  44. 44.
    Havens, A. M., Sun, H., Shiozawa, Y., Jung, Y., Wang, J., Mishra, A., et al. (2014). Human and murine very small embryonic-like cells represent multipotent tissue progenitors, in vitro and in vivo. Stem Cells and Development, 23(7), 689–701.PubMedCrossRefGoogle Scholar
  45. 45.
    Monti, M., Imberti, B., Bianchi, N., Pezzotta, A., Morigi, M., Del Fante, C., Redi, C. A., & Perotti, C. (2017). A novel method for isolation of pluripotent stem cells from human umbilical cord blood. Stem Cells and Development. doi: 10.1089/scd.2017.0012.PubMedGoogle Scholar
  46. 46.
    Bianchi, N., Longo, M., Redi, C., & Monti, M. (2017). Mammalian blastocyst mimicry. Molecular Reproduction & Development. doi: 10.1002/mrd.22862.Google Scholar
  47. 47.
    Ratajczak, J., Wysoczynski, M., Zuba-Surma, E., Wan, W., Kucia, M., Yoder, M. C., et al. (2011). Adult murine bone marrow-derived very small embryonic-like stem cells differentiate into the hematopoietic lineage after coculture over OP9 stromal cells. Experimental Hematology, 39(2), 225–237.PubMedCrossRefGoogle Scholar
  48. 48.
    Kim, Y., Jeong, J., Kang, H., Lim, J., Heo, J., Ratajczak, J., et al. (2014). The molecular nature of very small embryonic-like stem cells in adult tissues. International Journal of Stem Cells, 7(2), 55–62.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Mierzejewska, K., Heo, J., Kang, J. W., Kang, H., Ratajczak, J., Ratajczak, M. Z., et al. (2013). Genome-wide analysis of murine bone marrow–derived very small embryonic-like stem cells reveals that mitogenic growth factor signaling pathways play a crucial role in the quiescence and ageing of these cells. International Journal of Molecular Medicine, 32(2), 281–290.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Ratajczak, M. Z., Ratajczak, J., Suszynska, M., Miller, D. M., Kucia, M., Shin, D. M. (2017). A novel view of the adult stem cell compartment from the perspective of a quiescent population of very small embryonic-like stem cells. Circulation Research, 120(1), 166–178.PubMedCrossRefGoogle Scholar
  51. 51.
    Taichman, R. S., Wang, Z., Shiozawa, Y., Jung, Y., Song, J., Balduino, A., et al. (2010). Prospective identification and skeletal localization of cells capable of multilineage differentiation in vivo. Stem Cells and Development, 19(10), 1557–1570.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Shaikh, A., Bhartiya, D., Kapoor, S., & Nimkar, H. (2016). Delineating the effects of 5-fluorouracil and follicle-stimulating hormone on mouse bone marrow stem/progenitor cells. Stem Cell Research & Therapy, 7, 59.CrossRefGoogle Scholar
  53. 53.
    Abbott, A. (2013). Doubt cast over tiny stem cells. Nature, 499(7459), 390.PubMedCrossRefGoogle Scholar
  54. 54.
    Ratajczak, M. Z., Zuba-Surma, E., Wojakowski, W., Suszynska, M., Mierzejewska, K., Liu, R., et al. (2014). Very small embryonic-like stem cells (VSELs) represent a real challenge in stem cell biology: recent pros and cons in the midst of a lively debate. Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U. K., 28(3), 473–484.CrossRefGoogle Scholar
  55. 55.
    Suszynska, M., Zuba-Surma, E. K., Maj, M., Mierzejewska, K., Ratajczak, J., Kucia, M., et al. (2014). The proper criteria for identification and sorting of very small embryonic-like stem cells, and some nomenclature issues. Stem Cells and Development, 23(7), 702–713.PubMedCrossRefGoogle Scholar
  56. 56.
    Szade, K., Bukowska-Strakova, K., Nowak, W. N., Jozkowicz, A., & Dulak, J. (2014). Comment on: the proper criteria for identification and sorting of very small embryonic-like stem cells, and some nomenclature issues. Stem Cells and Development, 23(7), 714–716.PubMedCrossRefGoogle Scholar
  57. 57.
    Zuba-Surma, E. K., Kucia, M., Abdel-Latif, A., Dawn, B., Hall, B., Singh, R., Lillard, J. W. Jr., & Ratajczak, M. Z. (2008). Morphological characterization of very small embryonic-like stem cells (VSELs) by ImageStream system analysis. Journal of Cellular and Molecular Medicine, 12(1), 292–303.PubMedCrossRefGoogle Scholar
  58. 58.
    Bhartiya, D. (2017) Do adult somatic cells undergo reprogramming or endogenous pluripotent stem cells get activated to account for plasticity, regeneration and cancer initiation? Stem Cell Reviews. doi: 10.1007/s12015-017-9749-x.Google Scholar
  59. 59.
    Dezawa, M. (2016). Muse cells provide the pluripotency of mesenchymal stem cells: direct contribution of muse cells to tissue regeneration. Cell Transplantation, 25(5), 849–861.PubMedCrossRefGoogle Scholar
  60. 60.
    Kitada, M., Wakao, S., & Dezawa, M. (2012). Muse cells and induced pluripotent stem cell: implication of the elite model. Cellular and Molecular Life Sciences, 69(22), 3739–3750.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Bhartiya, D. (2013) Are mesenchymal cells indeed pluripotent stem cells or just stromal cells? OCT-4 and VSELs biology has led to better understanding. Stem Cells International. doi:  10.1155/2013/547501.Google Scholar
  62. 62.
    Parte, S., Bhartiya, D., Patel, H., Daithankar, V., Chauhan, A., Zaveri, K., et al. (2014). Dynamics associated with spontaneous differentiation of ovarian stem cells in vitro. Journal of Ovarian Research. doi: 10.1186/1757-2215-7-25.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Bhartiya, D., Shaikh, A., Nagvenkar, P., Kasiviswanathan, S., Pethe, P., Pawani, H., et al. (2012). Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy. Stem Cells and Development, 21(1), 1–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Shaikh, A., Nagvenkar, P., Pethe, P., Hinduja, I., & Bhartiya, D. (2015). Molecular and phenotypic characterization of CD133 and SSEA4 enriched very small embryonic-like stem cells in human cord blood. Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U. K., 9, 1909–1917.CrossRefGoogle Scholar
  65. 65.
    Shaikh, A., Anand, S., Kapoor, S., & Bhartiya, D. (2017). Mouse bone marrow VSELs exhibit differentiation into three embryonic germ lineages and hematopoietic & germ cells in culture. Stem Cell Reviews, 13(2), 202–216.PubMedCrossRefGoogle Scholar
  66. 66.
    Anand, S., Bhartiya, D., Sriraman, K., & Mallick, A. (2016). Underlying mechanisms that restore spermatogenesis on transplanting healthy niche cells in busulphan treated mouse testis. Stem Cell Reviews, 12(6), 682–697.PubMedCrossRefGoogle Scholar
  67. 67.
    Wang, J., Guo, X., Lui, M., Chu, P. J., Yoo, J., Chang, M., & Yen, Y. (2014). Identification of a distinct small cell population from human bone marrow reveals its multipotency in vivo and in vitro. PLoS One, 9(1), e85112. doi: 10.1371/journal.pone.0085112. eCollection 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Dimomeletis, I., Deindl, E., Zaruba, M., Groebner, M., Zahler, S., Laslo, S. M., David, R., Kostin, S., Deutsch, M. A., Assmann, G., Mueller-Hoecker, J., Feuring-Buske, M., & Franz, W. M. (2010). Assessment of human MAPCs for stem cell transplantation and cardiac regeneration after myocardial infarction in SCID mice. Experimental Hematology, 38(11), 1105–1114.PubMedCrossRefGoogle Scholar
  69. 69.
    Subramanian, K., Geraerts, M., Pauwelyn, K. A., Park, Y., Owens, D. J., Muijtjens, M., Ulloa-Montoya, F., Jiang, Y., Verfaillie, C. M., & Hu, W. S. (2010). Isolation procedure and characterization of multipotent adult progenitor cells from rat bone marrow. Methods in Molecular Biology, 636, 55–78.PubMedCrossRefGoogle Scholar
  70. 70.
    Wakao, S., Akashi, H., Kushida, Y., & Dezawa, M. (2014). Muse cells, newly found non-tumorigenic pluripotent stem cells, reside in human mesenchymal tissues. Pathology International, 64(1), 1–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Tsuchiyama, K., Wakao, S., Kuroda, Y., Ogura, F., Nojima, M., Sawaya, N., Yamasaki, K., Aiba, S., & Dezawa, M. (2013). Functional melanocytes are readily reprogrammable from multilineage-differentiating stress-enduring (muse) cells, distinct stem cells in human fibroblasts. The Journal of Investigative Dermatology, 133(10), 2425–2435.PubMedCrossRefGoogle Scholar
  72. 72.
    Heneidi, S., Simerman, A. A., Keller, E., Singh, P., Li, X., Dumesic, D. A., & Chazenbalk, G. (2013). Awakened by cellular stress: isolation and characterization of a novel population of pluripotent stem cells derived from human adipose tissue. PLoS One, 8(6), e64752.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Sriraman, K., Bhartiya, D., Anand, S., & Bhutda, S. (2015). Mouse ovarian very small embryonic-like stem cells resist chemotherapy and retain ability to initiate oocyte-specific differentiation. Reproductive Sciences, 22, 884–903.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Xiao, X., Chen, Z., Shiota, C., Prasadan, K., Guo, P., El-Gohary, Y., et al. (2013). No evidence for β cell neogenesis in murine adult pancreas. The Journal of Clinical Investigation, 123, 2207–2217.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Bhartiya, D., Mundekar, A., Mahale, V., & Patel, H. (2014). Very small embryonic-like stem cells are involved in regeneration of mouse pancreas post-pancreatectomy. Stem Cell Research Therapy. doi: 10.1186/scrt494.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Bhartiya, D., & Patel, H. (2016). Very small embryonic-like stem cells are involved in pancreatic regeneration and their dysfunction with age may lead to diabetes and cancer. Stem Cell Research Therapy. doi: 10.1186/s13287-015-0084-3.PubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Stem Cell Biology DepartmentIndian Council of Medical Research - National Institute for Research in Reproductive HealthMumbaiIndia

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