Table 1.

Stem cell types (in addition to Schwann Cells and olfactory ensheating cells) being explored as treatment strategies for neuroregeneration and repair in neurotrauma (SCI, TBI, and stroke).

	Source(s)	Potential progeny of differentiation	Benefits	Challenges	Specific examples of preclinical applications in neurotrauma (SCI, TBI, stroke)	Related references
Embryonic Stem Cells and Fetal Stem Cells	Inner cell mass from blastocysts (donated from left over embryos from in vitro fertilization), therapeutic cloning/somatic cell nuclear transfer, or existing cell lines—currently 390 NIH-approved hESC cell lines and 70 unapproved; donated fetal brain tissue, umbilical cord blood, bone marrow; donated fetal brain tissue, umbilical cord blood, bone marrow	Pluripotent: Neural stem cells (NSCs), neural progenitor cells (NPCs), neurons and neuronal subtypes (dopaminergic, GABA, and motor neurons), glial subtypes (astrocytes, oligodendrocytes); note—some fetal stem cell sources demonstrate multipotency, with more limited differentiation profiles [i.e., neural progenitor cells, neurons, and neuronal subtypes (GABA neurons), glial subtypes (astrocytes)]	Pluripotent; almost indefinite proliferation in vitro; potential for in vivo migration, region-specific differentiation, and structural recovery following cell transplantation of ESCs and/or ESC-derived; some evidence of cognitive, motor, and sensory recovery in animal models of SCI, TBI, and stroke	Ethical: derivation of ESCs from leftover IVF embryos and therapeutic cloning/somatic cell nuclear transfer; limited supply; Medical: risk of undifferentiated cells and tumorigenicity; immune rejection; Technical: isolation and expansion of cells derived from fetal sources may be difficult; Financial: high cost	SCI: (101–115) TBI: (116–122) Stroke: (123–133)	(134–148)
Adult Neural Stem Cells	Post-mortem or adult brain tissue biopsy (subgranular zone of hippocampus; subventricular zone of striatum)	Multipotent: Neurons and neuronal subtypes (GABA neurons); glial subtypes (astrocytes) NG2-expressing NSCs can stimulate the generation of oligodendrocytes	Potential source of autologous cell transplants; proliferation in vivo and in vitro; cell replacement, improved motor functionality, neuroprotection and immunomodulation; neutrotrophic support	Technical: difficult isolation from biopsy/autopsy sample low numbers esp. of potent cells	SCI: (149–153) TBI: (154); Stroke: (155)	(31, 93, 94, 156–166)
Induced Pluripotent Stem Cells (iPSCs)	Skin fibroblasts, melanocytes, adipocytes, CD34+ cells, human primary keratinocytes, umbilical cord blood (CD133+cells) and peripheral blood mononuclear cells	Pluripotent: Neural stem cells, neural progenitor cells, neurons and neuronal subtypes (dopaminergic, GABA, and motor neurons), glial subtypes (astrocytes, oligodendrocytes)	Plentiful and multiple adult somatic cell sources; source of autologous NPCs; potential to differentiate and migrate in vivo; evidence of neuron replacement; axonal myelination; local trophic support; inhibition of further cell death; improved behavioral outcomes in mouse models	Technical: major manufacturing hurdles; uncertainty about epigenetic memory of iPSCs; optimization of reprogramming methods; screening and removal of undifferentiated cells prior to and after transplant; Medical: mutations, tumorigenicity, teratoma formation	SCI: (105, 114, 167–173); TBI: (171, 174–177); Stroke: (178–188)	(144, 189–223)
Schwann Cells	Sural nerve	Schwann cells that myelinate host nerves	Ability to isolate and culture Schwann cells from sural nerve; reduced risk of tumorigencity in vivo; axonal regeneration and functional recovery	Technical: optimizing grafted Schwann Cell—host astrocyte interactions to facilitate greater axon regrowth	SCI: (73, 224–230); TBI: (231, 232)	(233–235
Olfactory Ensheating Cells	Glial cells and NPC populations in the olfactory bulb	Olfactory ensheating glia; small numbers of NPCs inside the olfactory bulb	Migration from CNS to PNS; enhancement of axonal growth; potentially autologous source of cells; functional improvement	Medical: inconsistent results in clinical trials; Technical: need to establish a safe and effective injection/delivery method	SCI: (236–244) TBI: (245–247) Stroke: (248–250)	(74, 246, 251–253)