Innovations_in_Molecular_Mechanisms_and_Tissue_Engineering_(Stem_Cell_Biology_and_Regenerative_Medicine)

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7.7.2 Oligodendrocyte Progenitor Cells

Oligodendrocyte progenitor cells (OPCs) are a subtype of glial cells found in the


CNS and are particularly prevalent in the hippocampus and neocortex [ 351 , 352 ].


The primary function of OPCs is to maintain oligodendrocyte populations, the


myelinating glia in the central nervous system [ 347 ]. Because of this, OPCs have


been used extensively as a method to produce myelin building blocks for repair of


injured white matter in rodent models of TBI and SCI [ 353 – 356 ]. Some groups have


found that injection of OPCs in spinal cord transplant experiments increased remy-


elination [ 357 , 358 ], with one group seeing these results only 7 days post-injury in


thoracic contusion SCI models [ 359 ]. OPC and oligodendrocyte-conditioned media


have been shown to increase axonal length and augment tissue sparing in vitro


[ 360 ]. Lastly, OPCs have been observed to survive, migrate, and differentiate into


adult oligodendrocytes after transplantation into a complete transection spinal cord


injury model [ 361 ]. Similarly, in the brain, OPCs transplanted into dysmyelinated


mouse brains differentiated into oligodendrocytes and signifi cantly increased axo-


nal myelination [ 353 ]. Similar effects were observed with induced pluripotent stem


cell (iPSC)-derived OPCs transplanted into a hypomyelinated mouse brain [ 362 ].


OPCs transplanted in a rodent model of periventricular leukomalacia not only sig-


nifi cantly increased myelination, but also increased proliferation of NPSCs and


decreased neuronal cell loss [ 351 ]. Nonetheless, there is currently no sustainable


source of OPCs , and OPC transplants are diffi cult to maintain at high phenotypic


purity, thus limiting current clinical translation [ 358 , 361 ].


7.7.3 Schwann Cells

Schwann cells are the myelinating cells of the peripheral nervous system that sus-


tain peripheral axon regeneration. Nonetheless, there is strong evidence suggesting


that Schwann cells can facilitate CNS axon regeneration as well. Schwann cells


have been shown to promote remyelination of CNS axons, reduce lesion cavitation,


and express various trophic factors when delivered via injection or biomaterial scaf-


fold into SCI lesions [ 210 , 363 – 365 ]. Further, Schwann cells are easily isolated


from peripheral nerves and expanded in vitro [ 363 ]. Some groups have found that


treatment of spinal cord transection with grafted Schwann cells was suffi cient to


allow damaged axons to extend into implanted grafts and become myelinated; how-


ever, the axons were unable to leave the grafts distally and re-innervate caudally


located tissues [ 366 – 368 ]. In a contusion SCI model, transplanted Schwann cells


signifi cantly reduced cavitation at the injury site and promoted remyelination of


endogenous axons growing into the graft [ 369 ]. Other studies have corroborated


fi ndings of reduced cavitation and further suggest that transplantation of Schwann


cells may promote tissue sparing and form a bridge across the lesion site [ 370 ]. It


has been postulated that the mechanism by which Schwann cells promote axonal


7 Regenerative Strategies for the Central Nervous System


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