Abstract
Nestin, a neural stem cell marker protein, is expressed in hair follicle cells above the bulge area. These nestin-positive hair follicle-associated-pluripotent (HAP) stem cells are negative for the keratinocyte marker K15 and can differentiate into neurons, glia, keratinocytes, smooth muscle cells, cardiac muscle cells, and melanocytes in vitro. HAP stem cells are positive for the stem cell marker CD34, as well as K15-negative, suggesting their relatively undifferentiated state. HAP stem cells promoted the functional recovery of injured peripheral nerves and the spinal cord. HAP stem cells differentiated into glial fibrillary acidic protein (GFAP)-positive Schwann cells when implanted in severed sciatic nerves and spinal cords in mice. These results suggest that HAP stem cells provide an important accessible, autologous source of adult stem cells for regenerative medicine, that have critical advantages over ES and iPS stem cells.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsSpringer Nature is developing a new tool to find and evaluate Protocols. Learn more
References
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
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
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
Amoh Y, Li L, Katsuoka K, Hoffman RM (2007) Chemotherapy targets the hair-follicle vascular network but not the stem cells. J Invest Dermatol 127:11–15
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
Hoffman RM (2014) Nestin-expressing hair follicle-accessible-pluripotent (HAP) stem cells for nerve and spinal cord repair. Cells Tissues Organs 200:42–47
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
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
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
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
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
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
Kajiura S, Mii S, Aki R, Hamada Y, Arakawa N, Kawahara K et al (2015) Cryopreservation of the hair follicle maintains pluripotency of nestin-expressing hair follicle-associated pluripotent stem cells. Tissue Eng Part C Methods 21:825–831
Yamauchi K, Yang M, Jiang P, Xu M, Yamamoto N, Tsuchiya H et al (2006) Development of real-time subcellular dynamic multicolor imaging of cancer-cell trafficking in live mice with a variable-magnification whole-mouse imaging system. Cancer Res 66:4208–4214
Amoh Y, Mii S, Aki R, Hamada Y, Kawahara K, Hoffman RM et al (2012) Multipotent nestin-expressing stem cells capable of forming neurons are located in the upper, middle and lower part of the vibrissa hair follicle. Cell Cycle 11:3513–3517
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
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this protocol
Cite this protocol
Amoh, Y., Katsuoka, K., Hoffman, R.M. (2016). Peripheral-Nerve and Spinal-Cord Regeneration in Mice Using Hair-Follicle-Associated Pluripotent (HAP) 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_4
Download citation
DOI: https://doi.org/10.1007/978-1-4939-3786-8_4
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3784-4
Online ISBN: 978-1-4939-3786-8
eBook Packages: Springer Protocols