Peripheral Nerve-Derived Stem Cell Spheroids Induce Functional Recovery and Repair after Spinal Cord Injury in Rodents

• Published in: International journal of molecular sciences Vol. 22; no. 8; p. 4141
• Main Authors: Lee, Hye-Lan, Yeum, Chung-Eun, Lee, HyeYeong, Oh, Jinsoo, Kim, Jong-Tae, Lee, Won-Jin, Ha, Yoon, Yang, Young-Il, Kim, Keung-Nyun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16-04-2021; MDPI
• Subjects: Adipocytes; Animals; Bone marrow; Cell differentiation; Cell therapy; Cells, Cultured; Collagen; Differentiation; Engraftment; functional recovery; Glia; Glial cells; Growth factors; Hydrogels; Injury prevention; Insulin; Morphology; Myelination; Nerve growth factor; Neural Stem Cells - cytology; Neurogenesis; Neuroglia; Neuronal-glial interactions; neuroregeneration; neurotrophic factor; Neurotrophic factors; Neurotrophin 3; peripheral nerve-derived stem cells; Peripheral nerves; Peripheral Nerves - cytology; Rats; Rats, Sprague-Dawley; Recovery of function; Regeneration; Schwann cells; Schwann Cells - cytology; Spheroids; Spheroids, Cellular - cytology; Spheroids, Cellular - transplantation; Spinal cord injuries; Spinal Cord Injuries - therapy; spinal cord injury; Spinal Cord Regeneration; Stem cell transplantation; Stem Cell Transplantation - methods; Stem cells; Transcription factors; spinal cord injury; peripheral nerve-derived stem cells; functional recovery; spheroids; neuroregeneration; neurotrophic factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22084141

Stem cell therapy is one of the most promising candidate treatments for spinal cord injury. Research has shown optimistic results for this therapy, but clinical limitations remain, including poor viability, engraftment, and differentiation. Here, we isolated novel peripheral nerve-derived stem cells (PNSCs) from adult peripheral nerves with similar characteristics to neural-crest stem cells. These PNSCs expressed neural-crest specific markers and showed multilineage differentiation potential into Schwann cells, neuroglia, neurons, and mesodermal cells. In addition, PNSCs showed therapeutic potential by releasing the neurotrophic factors, including glial cell-line-derived neurotrophic factor, insulin-like growth factor, nerve growth factor, and neurotrophin-3. PNSC abilities were also enhanced by their development into spheroids which secreted neurotrophic factors several times more than non-spheroid PNSCs and expressed several types of extra cellular matrix. These features suggest that the potential for these PNSC spheroids can overcome their limitations. In an animal spinal cord injury (SCI) model, these PNSC spheroids induced functional recovery and neuronal regeneration. These PNSC spheroids also reduced the neuropathic pain which accompanies SCI after remyelination. These PNSC spheroids may represent a new therapeutic approach for patients suffering from SCI.