Abstract
Chronic spinal cord injury (SCI) is a highly debilitating and recalcitrant disease with limited treatment options. Although various stem cell types have shown some clinical efficacy for injury repair they have not for SCI. Hair-follicle-associated pluripotent (HAP) stem cells have been shown to differentiate into neurons, Schwan cells, beating cardiomyocytes and many other type of cells, and have effectively regenerated acute spinal cord injury in mouse models. In the present report, HAP stem cells from C57BL/6J mice, encapsulated in polyvinylidene fluoride membranes (PFM), were implanted into the severed thoracic spinal cord of C57BL/6J or athymic nude mice in the early chronic phase. After implantation, HAP stem cells differentiated to neurons, astrocytes and oligodendrocytes in the regenerated thoracic spinal cord of C57BL/6J and nude mice. Quantitative motor function analysis, with the Basso Mouse Scale for Locomotion (BMS) score, demonstrated a significant functional improvement in the HAP-stem-cell-implanted mice, compared to non-implanted mice. HAP stem cells have critical advantages over other stem cells: they do not develop teratomas; do not loose differentiation ability when cryopreserved and thus are bankable; are autologous, readily obtained from anyone; and do not require genetic manipulation. HAP stem cells therefore have greater clinical potential for SCI repair than induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs)/neural progenitor cells (NPCs) or embryonic stem cells (ESCs). The present report demonstrates future clinical potential of HAP-stem-cell repair of chronic spinal cord injury, currently a recalcitrant disease.
Highlights
Spinal cord injury (SCI) is a severely debilitating and recalcitrant condition leading to neurological dysfunction, loss of independence, respiratory failure, psychological morbidities, and an increased mortality rate
We demonstrate that mouse hair-follicle-associated pluripotent (HAP) stem cells, encapsulated in polyvinylidene fluoride membranes (PFM), effected structural and functional regeneration of SCI in the early chronic phase when implanted in the injured spinal cord in mouse models
Fluorescence microscopy shows GFP-expressing PFM-encapsulated HAP stem cells growing as colonies in culture (Fig 2B)
Summary
Spinal cord injury (SCI) is a severely debilitating and recalcitrant condition leading to neurological dysfunction, loss of independence, respiratory failure, psychological morbidities, and an increased mortality rate. There is no effective treatment option to repair the injured spinal cord and restore lost function, including walking ability [2]. A variety of stem cells have been used to attempt to regenerate SCI, with only limited success [3, 4]. We discovered nestin-expressing stem cells in the bulge area of the hair follicle [5, 6]. We termed these cells hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from both mouse and human have multilineage differentiation capacity that could produce neurons, glia, smooth muscle cells, melanocytes, keratinocytes, cardiac muscle cells and dopaminergic neurons [7,8,9,10,11]
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