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Hair-Follicle-Associated Pluripotent (HAP) Stem Cells Encapsulated on Polyvinylidene Fluoride Membranes (PFM) Promote Functional Recovery from Spinal Cord Injury

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Abstract

Our previous studies showed that nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells, which reside in the bulge area of the hair follicle, could restore injured nerve and spinal cord and differentiate into cardiac muscle cells. Here we transplanted mouse green fluorescent protein (GFP)-expressing HAP stem-cell colonies enclosed on polyvinylidene fluoride membranes (PFM) into the severed thoracic spinal cord of nude mice. After seven weeks of implantation, we found the differentiation of HAP stem cells into neurons and glial cells. Our results also showed that PFM-captured GFP-expressing HAP stem-cell colonies assisted complete reattachment of the thoracic spinal cord. Furthermore, our quantitative motor function analysis with the Basso Mouse Scale for Locomotion (BMS) score demonstrated a significant improvement in the implanted mice compared to non-implanted mice with a severed spinal cord. Our study also showed that it is easy to obtain HAP stem cells, they do not develop teratomas, and do not loose differentiation ability when cryopreserved. Collectively our results suggest that HAP stem cells could be a better source compared to induced pluripotent stem cells (iPS) or embryonic stem (ES) cells for regenerative medicine, specifically for spinal cord repair.

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Acknowledgements

This work was partially supported by Grant-in-Aid for Scientific Research (C) 16 K10173 from the Ministry of Education, Science, Sports, and Culture of Japan, a grant from the Ministry of Education, Culture, Sports, Science, and Technology of the Japan Government, MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2014-2018), the Terumo Life Science Foundation (to Y. Amoh), and the Parents Association Grant of Kitasato University, School of Medicine (to K. Obara).

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Authors and Affiliations

  1. Department of Dermatology, Kitasato University School of Medicine, Minami Ward, Sagamihara, 252-0374, Japan

    Koya Obara, Natsuko Tohgi, Kyoumi Shirai, Sumiyuki Mii, Yuko Hamada, Nobuko Arakawa, Ryoichi Aki & Yasuyuki Amoh

  2. Basic Research Laboratory, National Cancer Institute, Frederick, MD, 21702, USA

    Shree Ram Singh

  3. AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, 92111, USA

    Robert M. Hoffman

  4. Department of Surgery, University of California, San Diego, CA, 92103, USA

    Robert M. Hoffman

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  1. Koya Obara
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  2. Natsuko Tohgi
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  3. Kyoumi Shirai
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  4. Sumiyuki Mii
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  5. Yuko Hamada
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  10. Yasuyuki Amoh
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Correspondence to Shree Ram Singh, Robert M. Hoffman or Yasuyuki Amoh.

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Obara, K., Tohgi, N., Shirai, K. et al. Hair-Follicle-Associated Pluripotent (HAP) Stem Cells Encapsulated on Polyvinylidene Fluoride Membranes (PFM) Promote Functional Recovery from Spinal Cord Injury. Stem Cell Rev and Rep 15, 59–66 (2019). https://doi.org/10.1007/s12015-018-9856-3

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