Human stem cells for CNS repair

Abstract

Although most peripheral tissues have at least a limited ability for self-repair, the central nervous system (CNS) has long been known to be relatively resistant to regeneration. Small numbers of stem cells have been found in the adult brain but do not appear to be able to affect any significant recovery following disease or insult. In the last few decades, the idea of being able to repair the brain by introducing new cells to repair damaged areas has become an accepted potential treatment for neurodegenerative diseases. This review focuses on the suitability of various human stem cell sources for such treatments of both slowly progressing conditions, such as Parkinson's disease, Huntington's disease and multiple sclerosis, and acute insult, such as stroke and spinal cord injury. Despite stem cell transplantation having now moved a step closer to the clinic with the first trials of autologous mesenchymal stem cells, the effects shown are moderate and are not yet at the stage of development that can fulfil the hopes that have been placed on stem cells as a means to replace degenerating cells in the CNS. Success will depend on careful investigation in experimental models to enable us to understand not just the practicalities of stem cell use, but also the underlying biological principles.

Stem/progenitor cells from bone marrow decrease neuronal death in global ischemia by modulation of inflammatory/immune responses

“…The results are consistent with previous reports that injection of MSCs into rodents protected against neuronal injury and reduced the neuronal death after permanent or transient focal ischemia (2)(3)(4)(5)23). The conclusion that MSCs produce antiimmune or immune-suppressive responses is consistent with numerous reports that the cells have similar effects in culture, in animal disease models, and in patients with graft-vs.-host disease (24)(25)(26)(27).…”

“…Administration of MSCs also produced beneficial effects in animal models for neurodegenerative diseases, such as Parkinson's disease, experimental autoimmune encephalomyelitis, and amyotrophic lateral sclerosis (2)(3)(4)(5). MSCs initially attracted interest for their ability to differentiate into multiple cellular phenotypes in culture and in vivo (1)(2)(3)(4)(5)(6)(7). However, recent observations indicate that only small numbers of the cells engraft into most injured tissues, and they disappear quickly (2)(3)(4)(5)(8)(9)(10).…”

“…MSCs initially attracted interest for their ability to differentiate into multiple cellular phenotypes in culture and in vivo (1)(2)(3)(4)(5)(6)(7). However, recent observations indicate that only small numbers of the cells engraft into most injured tissues, and they disappear quickly (2)(3)(4)(5)(8)(9)(10). When human MSCs (hMSCs) were injected into the dentate gyrus (DG) of the hippocampus in adult immunodeficient (ID) mice, most of the cells disappeared within 1 week, but they enhanced proliferation, migration, and neural differentiation of the endogenous neural stem cells (8).…”

Human Stem/Progenitor Cells from Bone Marrow Enhance Glial Differentiation of Rat Neural Stem Cells: A Role for Transforming Growth Factor β and Notch Signaling

“…The nonhematopoietic population of adult stem=progeni-tor cells from bone marrow referred to as mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) were shown to produce therapeutic effects in numerous animal models of neurodegenerative diseases, including cerebral ischemia, Parkinson's disease, multiple sclerosis, spinal cord injury, and traumatic brain injury [5][6][7][8][9][10]. Given their ability to home to multiple tissues, including the CNS, MSCs may be a viable means to stimulate the endogenous NSC population to assume a neuroprotective or neuroregenerative role.…”

Enrichment of putative stem cells from adipose tissue using dielectrophoretic field-flow fractionation

“…10,11 Recent experimental studies and clinical trials indicate that progenitor cells isolated from a range of adult tissues can stimulate angiogenesis in ischemic tissues and may preserve or rescue cardiac and neuronal function following ischemic insult. [12][13][14][15][16][17][18] In acute treatment scenarios, stem cells need to be harvested, processed, and administered promptly and within the context of existing interventional infrastructure. Moreover, for chronic or less acute maladies, stem cell based therapies are expected to enhance or perhaps even supplant many current orthopedic, plastic and general surgery approaches.…”