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

Obara, Koya; Tohgi, Natsuko; Shirai, Kyoumi; Mii, Sumiyuki; Hamada, Yuko; Arakawa, Nobuko; Aki, Ryoichi; Singh, Shree Ram; Hoffman, Robert M.; Amoh, Yasuyuki

doi:10.1007/s12015-018-9856-3

Cited by 10 publications

(12 citation statements)

References 48 publications

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“…Thoracic SCI was performed as described previously [ 17 ]: the thoracic spinal cord of nude or C57BL/6J mice was severed under anesthesia. The dorsal side of the thoracic vertebra of the mice was exposed, and a longitudinal incision of approximately 1.0 cm was made to the median.…”

Section: Methodsmentioning

confidence: 99%

“…Immunostaining was performed as described previously [ 17 ]: HAP stem cell colonies were cultured on Lab-Tek chamber slides, were incubated with the following antibodies: anti-βIII tubulin mouse monoclonal antibody (1:500, Tuj1clone; Covance, CA, USA); or anti-glial fibrillary acidic protein (GFAP) mouse monoclonal antibody (1:200; LAB VISION, CA, USA). The HAP stem cells were then incubated with goat anti-mouse IgG conjugated with Alexa Flour 568 ® (1:400, Molecular Probes, OR, USA) and 4’,6-diamino-2-phenylindole, dihydrochloride (DAPI) (Molecular Probes).…”

Section: Methodsmentioning

confidence: 99%

“…The spinal cord rejoined by HAP stem cells regained comprehensive hind-limb locomotor performance [ 14 , 15 ]. Recently we have shown that HAP stem cells encapsulated in polyvinylidene fluoride membranes (PFM) efficiently effected regeneration of the severed sciatic nerve and spinal cord in the acute phase in the C57BL/6J mouse model [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Chronic spinal cord injury functionally repaired by direct implantation of encapsulated hair-follicle-associated pluripotent (HAP) stem cells in a mouse model: Potential for clinical regenerative medicine

et al. 2022

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic spinal cord injury functionally repaired by direct implantation of encapsulated hair-follicle-associated pluripotent (HAP) stem cells in a mouse model: Potential for clinical regenerative medicine

et al. 2022

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“…Furthermore, other classes of stem cells for nerve tissue engineering are hair-follicleassociated pluripotent (HAP) Stem cells. Obara et al synthesized the polyvinylidene fluoride membrane encapsulated with HAP and implanted to the thoracic spinal cord of mice, which resulted in improvement and restoration of functional peripheral neurons (Obara et al 2019).…”

Section: Other Stem Cells For Neural Differentiationmentioning

confidence: 99%

Nanomaterial integration into the scaffolding materials for nerve tissue engineering: a review

Arzaghi

Adel

Jafari

et al. 2020

Reviews in the Neurosciences

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The nervous system, which consists of a complex network of millions of neurons, is one of the most highly intricate systems in the body. This complex network is responsible for the physiological and cognitive functions of the human body. Following injuries or degenerative diseases, damage to the nervous system is overwhelming because of its complexity and its limited regeneration capacity. However, neural tissue engineering currently has some capacities for repairing nerve deficits and promoting neural regeneration, with more developments in the future. Nevertheless, controlling the guidance of stem cell proliferation and differentiation is a challenging step towards this goal. Nanomaterials have the potential for the guidance of the stem cells towards the neural lineage which can overcome the pitfalls of the classical methods since they provide a unique microenvironment that facilitates cell–matrix and cell–cell interaction, and they can manipulate the cell signaling mechanisms to control stem cells’ fate. In this article, the suitable cell sources and microenvironment cues for neuronal tissue engineering were examined. Afterward, the nanomaterials that impact stem cell proliferation and differentiation towards neuronal lineage were reviewed.

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“…HF-MSCs can move down the hair shaft where they differentiated to internal HF (Turksen 2015 ). Special type of HF-MSCs was recently used to form cardiac muscle cells (Yamazaki et al 2016 ; Shirai et al 2017 ) and can fully repair the damaged sciatic nerve of mice (Obara et al 2019 ) and cortical dysplasia (Omidi et al 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Comparative characterization and osteogenic / adipogenic differentiation of mesenchymal stem cells derived from male rat hair follicles and bone marrow

2020

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Clinical applications of cell therapy and tissue regeneration under different conditions need a multiplicity of adult stem cell sources. Up to date, little is available on the comparative isolation, characterization, proliferation, rapid amplification, and osteogenic/adipogenic differentiation of rat mesenchymal stem cells (MSCs) isolated from living bulge cells of the hair follicle (HF) and bone marrow (BM) from the same animal. This work hopes to use HF-MSCs as an additional adult stem cell source for research and application. After reaching 80% confluence, the cell counting, viability %, and yields of HF-MSCs and BM-MSCs were nearly similar. The viability % was 91.41 ± 2.98 and 93.11 ± 3.06 while the cells yield of initial seeding was 33.15 ± 2.76 and 34.22 ± 3.99 and of second passage was 28.76 ± 1.01 and 29.56 ± 3.11 for HF-MSCs and BM-MSCs respectively. Clusters of differentiation (CDs) analysis revealed that HF-MSCs were positively expressed CD34, CD73 and CD200 and negatively expressed CD45. BM-MSCs were positively expressed CD73 and CD200 and negatively expressed of CD34 and CD45. The proliferation of HF-MSCs and BM-MSCs was determined by means of incorporation of Brd-U, population doubling time (PDT) assays and the quantity of formazan release. The percentage of Brd-U positive cells and PDT were relatively similar in both types of cells. The proliferation, as expressed by the quantity of formazan assay in confluent cells, revealed that the quantity of release by BM-MSCs was slightly higher than HF-MSCs. Adipogenic differentiated BM-MSCs showed moderate accumulation of oil red-O stained lipid droplets when compared to that of HF-MSCs which exhibited high stain. The total lipid concentration was significantly higher in adipogenic differentiated HF-MSCs than BM-MSCs (P < 0.05). It was found that activity of bone alkaline phosphatase and calcium concentration were significantly higher (P < 0.01 and P < 0.05 respectively) in osteogenic differentiated BM-MSCs than that of HF-MSCs. The present findings demonstrate that the HF-MSCs are very similar in most tested characteristics to BM-MSCs with the exception of differentiation. Additionally; no issues have been reported during the collection of HF-MSCs. Therefore, the HF may represent a suitable and accessible source for adult stem cells and can be considered an ideal cell source for adipogenesis research.

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

Cited by 10 publications

References 48 publications

Chronic spinal cord injury functionally repaired by direct implantation of encapsulated hair-follicle-associated pluripotent (HAP) stem cells in a mouse model: Potential for clinical regenerative medicine

Chronic spinal cord injury functionally repaired by direct implantation of encapsulated hair-follicle-associated pluripotent (HAP) stem cells in a mouse model: Potential for clinical regenerative medicine

Nanomaterial integration into the scaffolding materials for nerve tissue engineering: a review

Comparative characterization and osteogenic / adipogenic differentiation of mesenchymal stem cells derived from male rat hair follicles and bone marrow

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