論文

This paper describes human induced pluripotent stem (iPS) cell-derived neural stem cell (hiPSC-NSC) bundles covered with growth factor-encapsulated amphiphilic chitosan. The hiPSC-NSC bundle is formed by 4-12 hiPSC-NSC microfibers that are made by core-shell hydrogel microfibers encapsulating hiPSC-NSCs. The hiPSC-NSC microfibers can be cultured for over two weeks and induced to differentiate into neurons predominantly. We modified the coating material to make bundle structures that have growth factor enrichment capability (Figure 1). The coating material, amphiphilic chitosan, can release growth factors slowly for a long time, allowing hiPSC-NSCs to survive, grow and differentiate into neural lineages in the bundle structure. We believe that our hiPSC-NSC bundle would be an extremely effective tool for neural transplantation in neurodegenerative diseases such as stroke, spinal cord injury and peripheral nerve injury, because hiPSC-NSCs in the bundle structure have long-term survival ability in vivo.

The discovery of human induced pluripotent stem cells (iPSCs) has provided a model system for studying early events during human development. Developmentally melanocytes originate from migratory neural crest cells that emerge from the neural plate during embryogenesis after a complex process of differentiation, proliferation, and migration out of the neural tube along defined pathways. In the adult, human melanocytes are located in the basal layer of the epidermis, hair follicles, uvea, inner ear, and meninges. In the epidermis, melanocytes produce melanin pigment that gives color to the skin as well as providing protection from ultraviolet light damage. In addition, melanocytes transfer melanin pigment to hair matrix keratinocytes during each hair cycle to maintain hair pigmentation. Characterization of mouse melanocyte stem cells (MELSCs) is more complete than for humans. MELSCs are located in the bulge region of hair follicles, where hair follicle stem cells (HFSCs) also reside. Recently, it has been demonstrated that HFSCs provide a functional nice for MELSCs. According to current cancer stem cell theory, melanomas are considered to evolve from MELSCs, although the exact mechanism remains to be elucidated fully. In humans, importantly, the lack of more specific markers of MELSCs, current understanding of the molecular regulations of melanocyte development remains incomplete. Recently, the generation of melanocytes from iPSCs has lead to some clarification of human melanocyte development in vitro. Utilization of iPSC-derived melanocytes may prove invaluable in further study of human melanocytic development and novel therapies for patients suffering with pigmentation disorders and melanoma. © 2013 Springer Science+Business Media New York.

Stimulated by the 2012 Nobel Prize in Physiology or Medicine awarded for Shinya Yamanaka and Sir John Gurdon, there is an increasing interest in the iPS cells and reprogramming technologies in medical science. While iPS cells are expected to open new era providing enormous opportunities in the biomedical sciences in terms of cell therapies for regenerative medicine, safety-related concerns for iPS cell-based cell therapy should be resolved prior to the clinical application of iPS cells. In this symposium, the pre-clinical investigations of cell therapy for SCI using neural stem/progenitor cells derived from iPS cells, and their safety issues in vivo are outlined.