Novel Autologous Therapy for Long-Gap Peripheral Nerve Injury Using Human Sk-SCs
| Autor: | Maki Hirata, Tetsuro Tamaki, Masahiko Watanabe, Yoshiyasu Uchiyama, Nobuyuki Nakajima, Hiroyuki Hashimoto, Shuichi Soeda, Kosuke Saito |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology Macroglial Cells Cell Transplantation medicine.medical_treatment Nerve guidance conduit lcsh:Medicine Nervous System Mice 0302 clinical medicine Nerve Fibers Peripheral Nerve Injuries Animal Cells Medicine and Health Sciences Morphogenesis Blood and Lymphatic System Procedures Axon lcsh:Science Myelin Sheath Neurons Multidisciplinary Nerves Stem Cells Cell Differentiation Stem-cell therapy Anatomy Animal Models Muscle Differentiation Sciatic Nerve medicine.anatomical_structure Peripheral nerve injury Female Endoneurium Sciatic nerve Stem cell Cellular Types Muscle Regeneration Research Article medicine.medical_specialty Glial Cells Surgical and Invasive Medical Procedures Mouse Models Biology Research and Analysis Methods 03 medical and health sciences Model Organisms medicine Animals Humans Regeneration Cell Lineage Muscle Skeletal Transplantation lcsh:R Biology and Life Sciences Recovery of Function Cell Biology Axons Nerve Regeneration Disease Models Animal 030104 developmental biology Cellular Neuroscience lcsh:Q Schwann Cells Perineurium Organism Development 030217 neurology & neurosurgery Stem Cell Transplantation Developmental Biology Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 11, p e0166639 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk-SCs may be a practical source for autologous stem cell therapy following severe peripheral nerve injury. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|