Transplantation of stem cell-derived astrocytes for thetreatment of amyotrophic lateral sclerosis and spinal cordinjury

• 作者: Charles Nicaise Dinko Mitrecic Aditi Falnikar Angelo C Lepore
• 来源期刊: 世界干细胞杂志：英文版（电子版）
• 学科: 医学
• 关键词: Neuroprotection Stem CELL CELL therapy ASTROCYTE TRANSPLANTATION Amyotrophic lateral SCLEROSIS Spinal cord INJURY
• 年，卷（期）: 2015,（2）
• 页码范围: 380-398
• 页数: 19页
• 分类号: R

摘要

Neglected for years, astrocytes are now recognized tofulfill and support many, if not all, homeostatic functionsof the healthy central nervous system （CNS）. Duringneurodegenerative diseases such as amyotrophiclateral sclerosis （ALS） and spinal cord injury （SCI）,astrocytes in the vicinity of degenerating areasundergo both morphological and functional changesthat might compromise their intrinsic properties.Evidence from human and animal studies show thatdeficient astrocyte functions or loss-of-astrocytes largelycontribute to increased susceptibility to cell death forneurons, oligodendrocytes and axons during ALS andSCI disease progression. Despite exciting advances inexperimental CNS repair, most of current approachesthat are translated into clinical trials focus on thereplacement or support of spinal neurons throughstem cell transplantation, while none focus on thespecific replacement of astroglial populations. Knowingthe important functions carried out by astrocytesin the CNS, astrocyte replacement-based therapiesmight be a promising approach to alleviate overallastrocyte dysfunction, deliver neurotrophic support todegenerating spinal tissue and stimulate endogenousCNS repair abilities. Enclosed in this review, we gatheredexperimental evidence that argue in favor of astrocytetransplantation during ALS and SCI. Based on theirintrinsic properties and according to the cell typetransplanted, astrocyte precursors or stem cell-derivedastrocytes promote axonal growth, support mechanismsand cells involved in myelination, are able to modulatethe host immune response, deliver neurotrophic factorsand provide protective molecules against oxidative orexcitotoxic insults, amongst many possible benefits.Embryonic or adult stem cells can even be geneticallyengineered in order to deliver missing gene productsand therefore maximize the chance of neuroprotectionand functional recovery. However, before broad clinicaltranslation, further preclinical data on safety, reliabilityand therapeutic efficiency should be collected