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Human induced neural stem cells support functional recovery in spinal cord injury models

Zheng Jie|유승권|Son Daryeon|Kim In Yong|Kang Phil Jun|Park Kyoungmin|Priscilla Lia|Hong Wonjun|Yoon Byung Sun|Park Gyuman|Yoo Jeong-Eun|Song Gwonhwa|Lee Jang-Bo
생화학분자생물학회 (Korean Society Of Biochemistry And Molecular Biology)|2023.12|Experimental and Molecular Medicine|제55권 |pp. 1182-1192|DOI 10.1038/s12276-023-01003-2

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초록

Spinal cord injury (SCI) is a clinical condition that leads to permanent and/or progressive disabilities of sensory, motor, and autonomic functions. Unfortunately, no medical standard of care for SCI exists to reverse the damage. Here, we assessed the effects of induced neural stem cells (iNSCs) directly converted from human urine cells (UCs) in SCI rat models. We successfully generated iNSCs from human UCs, commercial fibroblasts, and patient-derived fibroblasts. These iNSCs expressed various neural stem cell markers and differentiated into diverse neuronal and glial cell types. When transplanted into injured spinal cords, UC-derived iNSCs survived, engrafted, and expressed neuronal and glial markers. Large numbers of axons extended from grafts over long distances, leading to connections between host and graft neurons at 8 weeks post-transplantation with significant improvement of locomotor function. This study suggests that iNSCs have biomedical applications for disease modeling and constitute an alternative transplantation strategy as a personalized cell source for neural regeneration in several spinal cord diseases.

Abstract

Spinal cord injury (SCI) is a clinical condition that leads to permanent and/or progressive disabilities of sensory, motor, and autonomic functions. Unfortunately, no medical standard of care for SCI exists to reverse the damage. Here, we assessed the effects of induced neural stem cells (iNSCs) directly converted from human urine cells (UCs) in SCI rat models. We successfully generated iNSCs from human UCs, commercial fibroblasts, and patient-derived fibroblasts. These iNSCs expressed various neural stem cell markers and differentiated into diverse neuronal and glial cell types. When transplanted into injured spinal cords, UC-derived iNSCs survived, engrafted, and expressed neuronal and glial markers. Large numbers of axons extended from grafts over long distances, leading to connections between host and graft neurons at 8 weeks post-transplantation with significant improvement of locomotor function. This study suggests that iNSCs have biomedical applications for disease modeling and constitute an alternative transplantation strategy as a personalized cell source for neural regeneration in several spinal cord diseases.

참고문헌 (48)

  1. Pereira, I. M., "Filling the gap: neural stem cells as a promising therapy for spinal cord injury", Pharmaceuticals (Basel), 12, pp.65~ (2019)
  2. Shao, A., "Crosstalk between stem cell and spinal cord injury : pathophysiology and treatment strategies", Stem Cell Res. Ther, 10, pp.238~ (2019)
  3. Fischer, I., "Transplanting neural progenitor cells to restore connectivity after spinal cord injury", Nat. Rev. Neurosci, 21, pp.366~383 (2020)
  4. Takagi, Y., "History of neural stem cell research and its clinical application", Neurol. Med. Chir. (Tokyo), 56, pp.110~124 (2016)
  5. Lu, P., "Long-distance growth and connectivity of neural stem cells after severe spinal cord injury", Cell, 150, pp.1264~1273 (2012)
  6. Lu, P., "Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury", Neuron, 83, pp.789~796 (2014)
  7. Sharp, K. G., "A re-assessment of long distance growth and connectivity of neural stem cells after severe spinal cord injury", Exp. Neurol, 257, pp.186~204 (2014)
  8. Kadoya, K., "Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration", Nat. Med, 22, pp.479~487 (2016)
  9. Rosenzweig, E. S., "Restorative effects of human neural stem cell grafts on the primate spinal cord", Nat. Med, 24, pp.484~490 (2018)
  10. Dulin, J. N., "Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts", Nat. Commun, 9, pp.84~ (2018)
  11. Hofstetter, C. P., "Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome", Nat. Neurosci, 8, pp.346~353 (2005)
  12. Cummings, B. J., "Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice", Proc. Natl. Acad. Sci. USA, 102, pp.14069~14074 (2005)
  13. Plemel, J. R., "Platelet-derived growth factor-responsive neural precursors give rise to myelinating oligodendrocytes after transplantation into the spinal cords of contused rats and dysmyelinated mice", Glia, 59, pp.1891~1910 (2011)
  14. Uchida, N., "Direct isolation of human central nervous system stem cells", Proc. Natl. Acad. Sci. USA, 97, pp.14720~14725 (2000)
  15. Jain, M, "GABAergic immunoreactivity is predominant in neurons derived from expanded human neural precursor cells in vitro", Exp. Neurol, 182, pp.113~123 (2003)
  16. Casarosa, S., "Neural stem cells: ready for therapeutic applications?", Mol. Cell. Ther, 2, pp.31~ (2014)
  17. Mothe, A., "Isolation of neural stem", progenitor cells from the periventricular region of the adult rat and human spinal cord, 2015, pp.1, e52732~
  18. Tang, Y., "Current progress in the derivation and therapeutic application of neural stem cells", Cell Death Dis, 8, pp.e3108~ (2017)
  19. Xu, J., "Direct lineage reprogramming : strategies, mechanisms, and applications", Cell Stem Cell, 16, pp.119~134 (2015)
  20. Wang, H., "Direct cell reprogramming : approaches, mechanisms and progress", Nat. Rev. Mol. Cell Biol, 22, pp.410~424 (2021)
  21. Curtis, E., "A first-in-human, Phase I study of neural stem cell transplantation for chronic spinal cord injury", Cell Stem Cell, 22, pp.941~950 (2018)
  22. Iwasaki, M., "Synergistic effects of self-assembling peptide and neural stem", progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury, 2014, pp.35, 2617~2629
  23. Shetty, A. K., "Grafted subventricular zone neural stem cells display robust engraftment and similar differentiation properties and form new neurogenic niches in the young and aged hippocampus", Stem Cells Transl. Med, 5, pp.1204~1215 (2016)
  24. Jin, M. C., "Stem cell therapies for acute spinal cord injury in humans : a review", Neurosurg. Focus, 46, pp.E10~ (2019)
  25. Anwar, M. A., "Inflammogenesis of secondary spinal cord injury", Front. Cell. Neurosci, 10, pp.98~ (2016)
  26. Robinson, J., "Optimization of trophic support for neural stem cell grafts in sites of spinal cord injury", Exp. Neurol, 291, pp.87~97 (2017)
  27. Kumamaru, H., "Generation and post-injury integration of human spinal cord neural stem cells", Nat. Methods, 15, pp.723~731 (2018)
  28. Kang, P. J., "mRNA-driven generation of transgene-free neural stem cells from human urine-derived cells", Cells, 8, pp.1043~ (2019)
  29. Li, W., "Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors", Proc. Natl. Acad. Sci. USA, 108, pp.8299~8304 (2011)
  30. Wang, Z., "High-strength and injectable supramolecular hydrogel selfassembled by monomeric nucleoside for tooth-extraction wound healing", Adv. Mater, 34, pp.e2108300~ (2022)
  31. Zhou, T., "Generation of induced pluripotent stem cells from urine", J. Am. Soc. Nephrol, 22, pp.1221~1228 (2011)
  32. Zhou, T., "Generation of human induced pluripotent stem cells from urine samples", Nat. Protoc, 7, pp.2080~2089 (2012)
  33. Zafarullah, M., "Urine-derived epithelial cell lines : a new tool to model Fragile X Syndrome(FXS)", Cells, 9, pp.2240~ (2020)
  34. Onifer, S. M., "In vitro labeling strategies for identifying primary neural tissue and a neuronal cell line after transplantation in the CNS", Cell Transplant, 2, pp.131~149 (1993)
  35. Vroemen, M., "Adult neural progenitor cell grafts survive after acute spinal cord injury and integrate along axonal pathways", Eur. J. Neurosci, 18, pp.743~751 (2003)
  36. Anderson, M. A., "Required growth facilitators propel axon regeneration across complete spinal cord injury", Nature, 561, pp.396~400 (2018)
  37. Jin, Y., "Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury", Exp. Neurol, 177, pp.265~275 (2002)
  38. Basso, D. M., "Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection", Exp. Neurol, 139, pp.244~256 (1996)
  39. Potas, J. R., "Augmented locomotor recovery after spinal cord injury in the athymic nude rat", J. Neurotrauma, 23, pp.660~673 (2006)
  40. Grath, A., "Direct cell reprogramming for tissue engineering and regenerative medicine", J. Biol. Eng, 13, pp.14~ (2019)
  41. Miller, C. B., "Impact of age on outcome of patients with cancer undergoing autologous bone marrow transplant", J. Clin. Oncol, 14, pp.1327~1332 (1996)
  42. Kusnierz-Glaz, C. R., "Influence of age on the outcome of 500 autologous bone marrow transplant procedures for hematologic malignancies", J. Clin. Oncol, 15, pp.18~25 (1997)
  43. Morizane, A., "Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate", Stem Cell Rep, 1, pp.283~292 (2013)
  44. Hallett, P. J., "Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson’s disease", Cell Stem Cell, 16, pp.269~274 (2015)
  45. Tao, Y., "Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys", Nat. Med, 27, pp.632~639 (2021)
  46. Takahashi, K., "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors", Cell, 126, pp.663~676 (2006)
  47. Liu, G., "Advances in pluripotent stem cells : history, mechanisms, technologies, and applications", Stem Cell Rev. Rep, 16, pp.3~32 (2020)
  48. Yamanaka, S., "Pluripotent stem cell-based cell therapy-promise and challenges", Cell Stem Cell, 27, pp.523~531 (2020)

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