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Introduction to Hair-Follicle-Associated Pluripotent Stem Cells

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Multipotent Stem Cells of the Hair Follicle

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1453))

Abstract

Nestin-expressing stem cells of the hair follicle, discovered by our laboratory, have been shown to be able to form outer-root sheaths of the follicle as well as neurons and many other non-follicle cell types. We have termed the nestin-expressing stem cells of the hair follicle as hair-follicle-associated pluripotent (HAP) stem cells. We have shown that the HAP stem cells from the hair follicle can effect the repair of peripheral nerve and spinal cord injury. The hair follicle stem cells differentiate into neuronal and glial cells after transplantation to the injured peripheral nerve and spinal cord, and enhance injury repair and locomotor recovery. When the excised hair follicle with its nerve stump was placed in Gelfoam® 3D histoculture, HAP stem cells grew and extended the hair follicle nerve which consisted of βIII-tubulin-positive fibers with F-actin expression at the tip. These findings indicate that βIII-tubulin-positive fibers elongating from the whisker follicle sensory nerve stump were growing axons. The growing whisker sensory nerve was highly enriched in HAP stem cells, which appeared to play a major role in its elongation and interaction with other nerves in 3D Gelfoam® histoculture, including the sciatic nerve, the trigeminal nerve, and the trigeminal nerve ganglion. These results suggest that a major function of the HAP stem cells in the hair follicle is for growth of the follicle sensory nerve. Recently, we have shown that HAP stem cells can differentiate into beating cardiac muscle cells. HAP stem cells have critical advantages for regenerative medicine over embryonic stem (ES) cells and induced pluripotent stem (iPS) cells in that they are highly accessible from each patient, thereby eliminating immunological issues since they are autologous, require no genetic manipulation, are non-tumorigenic, and do not present ethical issues.

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References

  1. Li L, Mignone J, Yang M, Matic M, Penman S, Enikolopov G et al (2003) Nestin expression in hair follicle sheath progenitor cells. Proc Natl Acad Sci U S A 100:9958–9961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mignone JL, Roig-Lopez JL, Fedtsova N, Schones DE, Manganas LN, Maletic-Savatic M et al (2007) Neural potential of a stem cell population in the hair follicle. Cell Cycle 6:2161–2170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yu H, Fang D, Kumar SM, Li L, Nguyen TK, Acs G et al (2006) Isolation of a novel population of multipotent adult stem cells from human hair follicles. Am J Pathol 168:1879–1888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Morris RJ, Liu Y, Marles L, Yang Z, Trempus C, Li S et al (2004) Capturing and profiling adult hair follicle stem cells. Nat Biotechnol 22:411–417

    Article  CAS  PubMed  Google Scholar 

  5. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M et al (2004) Defining the epithelial stem cell niche in skin. Science 303:359–363

    Article  CAS  PubMed  Google Scholar 

  6. Rhee H, Polak L, Fuchs E (2006) Lhx2 maintains stem cell character in hair follicles. Science 312:1946–1949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Amoh Y, Li L, Katsuoka K, Penman S, Hoffman RM (2005) Multipotent nestin-positive, keratin-negative hair-follicle-bulge stem cells can form neurons. Proc Natl Acad Sci U S A 102:5530–5534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Amoh Y, Kanoh M, Niiyama S, Kawahara K, Satoh Y, Katsuoka K et al (2009) Human and mouse hair follicles contain both multipotent and monopotent stem cells. Cell Cycle 8:176–177

    Article  CAS  PubMed  Google Scholar 

  9. Hoffman RM (2006) The pluripotency of hair follicle stem cells. Cell Cycle 5:232–233

    Article  CAS  PubMed  Google Scholar 

  10. Yashiro M, Mii S, Aki R, Hamada Y, Arakawa N, Kawahara K et al (2015) From hair to heart: nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells differentiate to beating cardiac muscle cells. Cell Cycle 14:2362–2366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sieber-Blum M, Grim M, Hu YF, Szeder V (2004) Multipotent neural crest stem cells in the adult hair follicle. Dev Dyn 231:258–269

    Article  CAS  PubMed  Google Scholar 

  12. Sieber-Blum M, Schnell L, Grim M, Hu YF, Schneider R, Schwab ME (2006) Characterization of epidermal neural crest stem cell (EPI-NCSC) grafts in the lesioned spinal cord. Mol Cell Neurosci 32:67–81

    Article  CAS  PubMed  Google Scholar 

  13. Biernaskie J, Paris M, Morozova O, Fagan BM, Marra M, Pevny L et al (2009) SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells. Cell Stem Cell 5:610–623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Amoh Y, Li L, Yang M, Moossa AR, Katsuoka K, Penman S et al (2004) Nascent blood vessels in the skin arise from nestin-expressing hair follicle cells. Proc Natl Acad Sci U S A 101:13291–13295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Amoh Y, Li L, Katsuoka K, Hoffman RM (2008) Multipotent hair follicle stem cells promote repair of spinal cord injury and recovery of walking function. Cell Cycle 7:1865–1869

    Article  CAS  PubMed  Google Scholar 

  16. Amoh Y, Kanoh M, Niiyama S, Hamada Y, Kawahara K, Sato Y et al (2009) Human hair follicle multipotent stem (hfPS) cells promote regeneration of peripheral-nerve injury: an advantageous alternative to ES and iPS cells. J Cell Biochem 107:1016–1020

    Article  CAS  PubMed  Google Scholar 

  17. Amoh Y, Hamada Y, Aki R, Kawahara K, Hoffman RM, Katsuoka K (2010) Direct transplantation of uncultured hair-follicle multipotent stem (hfPS) cells promotes the recovery of peripheral nerve injury. J Cell Biochem 110:272–277

    CAS  PubMed  Google Scholar 

  18. Li L, Margolis LB, Hoffman RM (1991) Skin toxicity determined in vitro by three-dimensional, native-state histoculture. Proc Natl Acad Sci U S A 88:1908–1912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yu H, Kumar SM, Kossenkov AV, Showe L, Xu X (2010) Stem cells with neural crest characteristics derived from the bulge region of cultured human hair follicles. J Invest Dermatol 130:1227–1236

    Article  CAS  PubMed  Google Scholar 

  20. Amoh Y, Li L, Campillo R, Kawahara K, Katsuoka K, Penman S et al (2005) Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves. Proc Natl Acad Sci U S A 102:17734–17738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Liu F, Uchugonova A, Kimura H, Zhang C, Zhao M, Zhang L et al (2011) The bulge area is the major hair follicle source of nestin-expressing multipotent stem cells which can repair the spinal cord compared to the dermal papilla. Cell Cycle 10:830–839

    Article  CAS  PubMed  Google Scholar 

  22. Uchugonova A, Duong J, Zhang N, König K, Hoffman RM (2011) The bulge area is the origin of nestin-expressing multipotent stem cells of the hair follicle. J Cell Biochem 112:2046–2050

    Article  CAS  PubMed  Google Scholar 

  23. Uchugonova A, Hoffman RM, Weinigel M, Koenig K (2011) Watching stem cells in the skin of living mice noninvasively. Cell Cycle 10:2017–2020

    Article  CAS  PubMed  Google Scholar 

  24. Duong J, Mii S, Uchugonova A, Liu F, Moossa AR, Hoffman RM (2012) Real-time confocal imaging of trafficking of nestin-expressing multipotent stem cells in mouse whiskers in long-term 3-D histoculture. In Vitro Cell Dev Biol Anim 48:301–305

    Article  CAS  PubMed  Google Scholar 

  25. Liu F, Zhang C, Hoffman RM (2014) Nestin-expressing stem cells from the hair follicle can differentiate into motor neurons and reduce muscle atrophy after transplantation to injured nerves. Tissue Eng 20:656–662

    CAS  Google Scholar 

  26. Mii S, Duong J, Tome Y, Uchugonova A, Liu F, Amoh Y et al (2013) The role of hair follicle nestin-expressing stem cells during whisker sensory-nerve growth in long-term 3D culture. J Cell Biochem 114:1674–1684

    Article  CAS  PubMed  Google Scholar 

  27. Okano H, Nakamura M, Yoshida K, Okada Y, Tsuji O, Nori S et al (2013) Steps toward safe cell therapy using induced pluripotent stem cells. Circ Res 112:523–533

    Article  CAS  PubMed  Google Scholar 

  28. Nori S, Okada Y, Yasuda A, Tsuji O, Takahashi Y, Kobayashi Y et al (2011) Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. Proc Natl Acad Sci U S A 108:16825–16830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Keirstead HS, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K et al (2005) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 25:4694–4705

    Article  CAS  PubMed  Google Scholar 

  30. Sakaue M, Sieber-Blum M (2015) Human epidermal neural crest stem cells as a source of Schwann cells. Development 142:3188–3197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mii S, Amoh Y, Katsuoka K, Hoffman RM (2014) Comparison of nestin-expressing multipotent stem cells in the tongue fungiform papilla and vibrissa hair follicle. J Cell Biochem 115:1070–1076

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Robert M. Hoffman .

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Hoffman, R.M. (2016). Introduction to Hair-Follicle-Associated Pluripotent Stem Cells. In: Hoffman, R. (eds) Multipotent Stem Cells of the Hair Follicle. Methods in Molecular Biology, vol 1453. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3786-8_1

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  • DOI: https://doi.org/10.1007/978-1-4939-3786-8_1

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3784-4

  • Online ISBN: 978-1-4939-3786-8

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