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Isolation and Characterization of a Fetal-Maternal Microchimeric Stem Cell Population in Maternal Hair Follicles Long after Parturition

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Abstract

Fetal-maternal microchimerism describes the acquisition of fetal stem cells (FSC) by the mother during pregnancy and their long-term persistence after parturition. FSC may engraft in a variety of maternal tissues especially if there is organ/tissue injury, but their role and mechanism of persistence still remains elusive. Clinical applications due to their pluripotency, immunomodulatory effects and accessibility make them good candidates for ex-vivo manipulation and autologous therapies. The hair follicles contain a distinctive niche for pluripotent stem cells (PSC). To date, there is no published evidence of fetal microchimerism in the hair follicle. In our study, follicular unit extraction (FUE) technique allowed easy stem cell cultures to be obtained while simple hair follicle removal by pull-out technique failed to generate stem cells in culture. We identified microchimeric fetal stem cells within the primitive population of maternal stem cells isolated from the hair follicles with typical mesenchymal phenotype, expression of PSC genes and differentiation potential towards osteocytes, adypocites and chondrocytes. This is the first study to isolate fetal microchimeric stem cells in adult human hair long after parturition. We presume a sanctuary partition mechanism with PSC of the mother deposited during early embryogenesis could explain their long-term persistence.

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References

  1. Levy, V., Lindon, C., Harfe, B. D., & Morgan, B. A. (2005). Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Developmental Cell, 9, 855–861. https://doi.org/10.1016/j.devcel.2005.11.003.

    Article  CAS  PubMed  Google Scholar 

  2. Hong, Y. C., Liu, H. M., Chen, P. S., et al. (2007). Hair follicle: a reliable source of recipient origin after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplantation, 40(9), 871–874.

    Article  CAS  PubMed  Google Scholar 

  3. Yu, H., Fang, D., Kumar, S. M., et al. (2006). Isolation of a novel population of multipotent adult stem cells from human hair follicles. The American Journal of Pathology, 168, 1879–1888. https://doi.org/10.2353/ajpath.2006.051170.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Boddy, A. M., Fortunato, A., Wilson Sayres, M., & Aktipis, A. (2015). Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb. Bioessays, 37(10), 1106–1118.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Magued, M., Hamdi, H., & Welsh, J. (2008). High frequency of fetal cells within a primitive stem cell population in maternal blood. Human Reproduction, 23(4), 928–933.

    Article  Google Scholar 

  6. Ratajczak, M., Machalinski, B., Wojakowski, W., Ratajczak, J., & Kucia, M. (2007). A hypothesis for an embryonic origin of pluripotent Oct-4 + stem cells in adult bone marrow and other tissues. Leukemia, 21, 860–867.

    Article  CAS  PubMed  Google Scholar 

  7. Cismaru, C. A., Pop, L., & Berindan-Neagoe, I. (2018). Incognito: Are Microchimeric Fetal Stem Cells that Cross Placental Barrier Real Emissaries of Peace? Stem Cell Reviews, 2018. https://doi.org/10.1007/s12015-018-9834-9.

  8. Shimazaki, C., Ochiai, N., Uchida, R., et al. (2002). Non-T cell-depleted HLA haploidentical stem cell transplantation in advanced hematologic malignancies based on the feto-maternal michrochimerism. Blood, 101(8), 3334–3336.

    Article  CAS  PubMed  Google Scholar 

  9. Fugazzola, L., Cirello, V., & Beck-Peccoz, P. (2011). Fetal microchimerism as an explanation of disease. Nature Reviews Endocrinology, 7, 89–97.

    Article  CAS  PubMed  Google Scholar 

  10. Kucia, M., Reca, R., Campbell, F. R., et al. (2006). A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+ stem cells identified in adult bone marrow. Leukemia, 20, 857–869.

    Article  CAS  PubMed  Google Scholar 

  11. Kucia, M., Halasa, M., Wysoczynski, M., et al. (2007). Morphological and molecular characterization of novel population of CXCR4 + SSEA-4 + Oct-4+ very small embryonic-like (VSEL) cells purified from human cord blood – preliminary report. Leukemia, 21, 297–303.

    Article  CAS  PubMed  Google Scholar 

  12. Kruse, C., Kajahn, J., Petschnik, A. E., et al. (2006). Adult pancreatic stem/progenitor cells spontaneously differentiate in vitro into multiple cell lineages and form teratoma-like structures. Annals of Anatomy, 188, 503–517.

    Article  CAS  PubMed  Google Scholar 

  13. Guan, K., Nayernia, K., Maier, L. S., et al. (2006). Pluripotency of spermatogonial stem cells from adult mouse testis. Nature, 440, 1199–1203.

    Article  CAS  PubMed  Google Scholar 

  14. Ling, T. Y., Kuo, M. D., Li, C. L., et al. (2006). Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro. Proceedings of the National Academy of Sciences of the United States of America, 103, 9530–9535.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448(7151), 313–317.

    Article  CAS  PubMed  Google Scholar 

  16. Kim, J. B., Sebastiano, V., Wu, G., et al. (2009). Oct4-induced pluripotency in adult neural stem cells. Cell., 136(3), 411–419.

    Article  CAS  PubMed  Google Scholar 

  17. Mihu, C. M., Rus Ciuca, D., Soritau, O., Susman, S., & Mihu, D. (2009). Isolation and characterization of mesenchymal stem cells from the amniotic membrane. Romanian Journal of Morphology and Embryology, 50(1), 73–77.

    PubMed  Google Scholar 

  18. Pochampally, R. R., Smith, J. R., Ylostalo, J., & Prockop, D. J. (2004). Serum deprivation of human marrow stromal cells (hMSCs) selects for a subpopulation of early progenitor cells with enhanced expression of OCT-4 and other embryonic genes. Blood, 103, 1647–1652.

    Article  CAS  PubMed  Google Scholar 

  19. Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418, 41–49.

    Article  CAS  PubMed  Google Scholar 

  20. D’Ippolito, G., Diabira, S., Howard, G. A., Menei, P., Roos, B. A., & Schiller, P. C. (2004). Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. Journal of Cell Science, 117, 2971–2981.

    Article  CAS  PubMed  Google Scholar 

  21. Kogler, G., Sensken, S., Airey, J. A., et al. (2004). A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. The Journal of Experimental Medicine, 200, 123–135.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Nayernia, K., Lee, J. H., Drusenheimer, N., et al. (2006). Derivation of male germ cells from bone marrow stem cells. Laboratory Investigation, 86, 654–663.

    Article  CAS  PubMed  Google Scholar 

  23. Johnson, J., Bagley, J., Skaznik-Wikiel, M., et al. (2005). Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell, 122, 303–315.

    Article  CAS  PubMed  Google Scholar 

  24. Maloney, S., Smith, A., Furst, D. E., et al. (1999). Microchimerism of maternal origin persists into adult life. The Journal of Clinical Investigation, 104, 41–47.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Lo, Y. M., Lo, E. S., Watson, N., Noakes, L., Sargent, I. L., Thilaganathan, B., & Wainscoat, J. S. (1996). Twoway cell traffic between mother and fetus: biologic and clinical implications. Blood, 88, 4390–4395.

    CAS  PubMed  Google Scholar 

  26. Virchow, R. (1855). Editorial Archive fuer pathologische. Anatomie und Physiologie fuer klinische Medizin, 8, 23–54.

    Google Scholar 

  27. Rovó, A., Meyer-Monard, S., Heim, D., et al. (2005). No evidence of plasticity in hair follicles of recipients after allogeneic hematopoietic stem cell transplantation. Experimental Hematology, 33(8), 909–911.

    Article  CAS  PubMed  Google Scholar 

  28. Santurtún, A., Riancho, J. A., Santurtún, M., et al. (2017). Genetic DNA profile in urine and hair follicles from patients who have undergone allogeneic hematopoietic stem cell transplantation. Science & Justice, 57(5), 336–340.

    Article  Google Scholar 

  29. Li, Y. T., Xie, M. K., & Wu, J. (2014). DNA profiling in peripheral blood, buccal swabs, hair follicles and semen from a patient following allogeneic hematopoietic stem cells transplantation. Biomed Rep, 2(6), 804–808.

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Kaiser, S., Hackanson, B., Follo, M., et al. (2007). BM cells giving rise to MSC in culture have heterogeneous CD34 and CD45 phenotype. Cytotherapy, 9, 439–450.

    Article  CAS  PubMed  Google Scholar 

  31. Jacewicz, R., Lewandowski, K., Rupa-Matysek, J., et al. (2010). Donor-derived DNA in hair follicles of recipients after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplantation, 45(11), 1638–1644.

    Article  CAS  PubMed  Google Scholar 

  32. Ventura Ferreira, M. S., Bienert, M., Müller, K., et al. (2018). Comprehensive characterization of chorionic villi-derived mesenchymal stromal cells from human placenta. Stem Cell Research & Therapy, 9, 28.

    Article  CAS  Google Scholar 

  33. Jay Iams, Creasy, Robert K., Resnik, Robert, Resnik, Robert (2004). Maternal-fetal medicine. Philadelphia: W.B. Saunders Co. pp. 31–32. ISBN 0-7216-0004-2.

  34. Lash, G., Robson, S., & Bulmer, J. (2010). Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua. Placenta., 31(S), 87–92. https://doi.org/10.1016/j.placenta.2009.12.022.

    Article  CAS  Google Scholar 

  35. Lamar, D. L., Weyand, C. M., & Goronzy, J. J. (2010). Promoter choice and translational repression determine cell type–specific cell surface density of the inhibitory receptor CD85j expressed on different hematopoietic lineages. Blood., 115(16), 3278–3286.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Colonna, M., Samaridis, J., Cella, M., et al. (1998). Cutting Edge: Human Myelomonocytic Cells Express an Inhibitory Receptor for Classical and Nonclassical MHC Class I Molecules. Journal of Immunology, 160, 3096–3100.

    CAS  Google Scholar 

  37. Steven, A., & Seliger, B. (2018). The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer. Breast Care (Basel), 13(1), 16–21.

    Article  Google Scholar 

  38. Di Cristofaro, J., Karlmark, K. R., Kanaan, S. B., et al. (2018). Soluble HLA-G Expression Inversely Correlates With Fetal Microchimerism Levels in Peripheral Blood From Women With Scleroderma. Frontiers in Immunology, 9, 1685.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Cirello, V., Recalcati, M. P., Muzza, M., et al. (2008). Fetal cell microchimerism in papillary thyroid cancer: a possible role in tumor damage and tissue repair. Cancer Research, 15, 8482–8488.

    Article  CAS  Google Scholar 

  40. Gyurkocza, B., & Sandmaier, B. M. (2014). Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood., 124(3), 344–353.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Cell Trialists’ Collaborative Group. (2005). Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. Journal of Clinical Oncology, 23(22), 5074–5087.

    Article  Google Scholar 

  42. Zhang, H., Chen, J., & Que, W. (2012). Allogeneic peripheral blood stem cell and bone marrow transplantation for hematologic malignancies: meta-analysis of randomized controlled trials. Leukemia Research, 36(4), 431–437.

    Article  PubMed  Google Scholar 

  43. Okada, M., Yoshihara, S., Taniguchi, K., et al. (2012). Intrabone Marrow Transplantation of Unwashed Cord Blood Using Reduced-Intensity Conditioning Treatment: A Phase I Study. Biology of Blood and Marrow Transplantation, 18, 633–639.

    Article  PubMed  Google Scholar 

  44. Toprak, S. K. (2018). Donor lymphocyte infusion in myeloid disorders. Transfusion and Apheresis Science, 57(2), 178–186.

    Article  PubMed  Google Scholar 

  45. Krampera, M., Glennie, S., Dyson, J., et al. (2003). Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood, 101(9), 3722–3729.

    Article  CAS  PubMed  Google Scholar 

  46. Yu, J., Ren, X., Cao, S., Li, H., & Hao, X. (2008). Beneficial effects of fetal-maternal microchimerism on the activated haplo-identical peripheral blood stem cell treatment for cancer. Cytotherapy, 10(4), 331–339.

    Article  CAS  PubMed  Google Scholar 

  47. Ying H, Jinpu Y, Shui C, et al. (2010). Fetal–Maternal Microchimerism Enhances the Survival Effect of Interleukin-2-Activated Haploidentical Peripheral Blood Stem Cell Treatment in Patients with Advanced Solid Cancer. Cancer Biotherapy and Radiopharmaceuticals, 25(6, Mary Ann Liebert, Inc.).

  48. Corcione, A., Benvenuto, F., Ferretti, E., et al. (2006). Human mesenchymal stem cells modulate B cell functions. Blood, 2006(107), 367–372. https://doi.org/10.1182/blood-2005-07-2657.

    Article  CAS  Google Scholar 

  49. Wang, L., Zhu, C., Ma, D., et al. (2018). Efficacy and safety of mesenchymal stromal cells for the prophylaxis of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials. Annals of Hematology, 97, 1941.

    Article  PubMed  Google Scholar 

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Acknowledgements

Part of the research was supported from the grant 108BG 01/10/2016) PN-III-P2-2.1-BG-2016-0117 directed by Assoc. prof. Sergiu Susman. The the work was done at the Research Center for Functional Genomics, Biomedicine and Translational Medicine of the University of Medicine and Pharmacy Iuliu Hatieganu.

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Authors and Affiliations

  1. Research Center for Functional Genomics Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Cosmin Andrei Cismaru, Ancuta - Maria Jurj, Raduly Lajos & Ioana Berindan Neagoe

  2. The Oncology Institute “Prof. Dr. Ion Chiricuta”, Cluj-Napoca, Romania

    Cosmin Andrei Cismaru, Olga Soritau, Bogdan Pop, Cosmina Bocean, Oana Baldasici & Ioana Berindan Neagoe

  3. Department of Dermatology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Bogdan Albzour

  4. Research Center for Advanced Medicine – Medfuture, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Cristian Moldovan & Ioana Berindan Neagoe

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  1. Cosmin Andrei Cismaru
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  2. Olga Soritau
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Correspondence to Cosmin Andrei Cismaru.

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The study was approved by the ethics committee of the University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca, reg. no. 100/08.03.2017.

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All authors have read and approved this version of the article, and due care has been taken to ensure the integrity of the work. No part of this article has been published or submitted elsewhere. No financial conflict of interest exists in the submission of this manuscript.

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Cismaru, C.A., Soritau, O., Jurj, A . et al. Isolation and Characterization of a Fetal-Maternal Microchimeric Stem Cell Population in Maternal Hair Follicles Long after Parturition. Stem Cell Rev and Rep 15, 519–529 (2019). https://doi.org/10.1007/s12015-019-09885-4

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