Despite intensive efforts in the field of peripheral nerve injury and regeneration, it remains difficult to achieve full functional recovery in humans following extended peripheral nerve lesions. In this study, the authors examined the use of blood-derived CD133+ cells in promoting the repair of peripheral nerve defects.
The authors transplanted phosphate-buffered saline (control), mononuclear cells, or CD133+ cells embedded in atelocollagen gel into a silicone tube that was used to bridge a 15-mm defect in the sciatic nerve of athymic rats (12 animals in each group). At 8 weeks postsurgery, molecular, histological, and functional evaluations were performed in regenerated tissues.
The authors found that sciatic nerves in which a defect had been made were structurally and functionally regenerated within 8 weeks after CD133+ cell transplantation. From macroscopic evaluation, massive nervelike tissues were confirmed only in rats with CD133+ cell transplantation compared with the other groups. Morphological regeneration in the samples after CD133+ cell transplantation, as assessed using toluidine blue staining, was enhanced significantly in terms of the number of myelinated fibers, axon diameter, myelin thickness, and percentage of neural tissue. Compound muscle action potentials were observed only in CD133+ cell–treated rats. Furthermore, it was demonstrated that the transplanted CD133+ cells differentiated into Schwann cells by 8 weeks after transplantation.
The results show that CD133+ cells have potential for enhancement of histological and functional recovery from peripheral nerve injury. This attractive cell source could be purified easily from peripheral blood and could be a feasible autologous candidate for peripheral nerve injuries in the clinical setting.
CopelmanCACuznerMLGroomeNDiemelLT: Temporal analysis of growth factor mRNA expression in myelinating rat brain aggregate cultures: increments in CNTF, FGF-2, IGFI, and PDGF-AA mRNA are induced by antibody-mediated demyelination. Glia30:342–3512000
GallacherLMurdochBWuDMKaranuFNKeeneyMBhatiaM: Isolation and characterization of human CD34(-)Lin(-) and CD34(+)Lin(-) hematopoietic stem cells using cell surface markers AC133 and CD7. Blood95:2813–28202000
GoussetisETheodosakiMPaterakisGPeristeriJPetropoulosDKitraV: A functional hierarchy among the CD34+ hematopoietic cells based on in vitro proliferative and differentiative potential of AC133+CD34(bright) and AC133(dim/)-CD34+ human cord blood cells. J Hematother Stem Cell Res9:827–8402000
IwasakiHKawamotoAIshikawaMOyamadaANakamoriSAsaharaT: Dose-dependent contribution of CD34-positive cell transplantation to concurrent vasculogenesis and cardiomyogenesis for functional regenerative recovery after myocardial infarction. Circulation113:1311–13252006
MajkaMJanowska-WieczorekARatajczakJEhrenmanKPietrzkowskiZKowalskaMA: Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood97:3075–30852001
MatsumotoTKawamotoAKurodaRIshikawaMMifuneYAsaharaT: Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing. Am J Pathol169:1440–14572006
NilssonADahlinLLundborgGKanjeM: Graft repair of a peripheral nerve without the sacrifice of a healthy donor nerve by the use of acutely dissociated autologous Schwann cells. Scand J Plast Reconstr Surg Hand Surg39:1–62005