Combination of BMSCs‐laden acellular nerve xenografts transplantation and G‐CSF administration promotes sciatic nerve regeneration

Abstract

Peripheral nerve gaps often lead to interrupted innervation, manifesting as severe sensory and motor dysfunctions. The repairs of the nerve injuries have not achieved satisfactory curative effects in clinic. The transplantation of bone marrow stromal cells (BMSCs)-laden acellular nerve xenografts (ANX) has been proven more effective than the acellular nerve allografting. Besides, granulocyte colony-stimulating factor (G-CSF) can inhibit inflammation and apoptosis, and thus is conducive to the microenvironmental improvement of axonal regeneration. This study aims to investigate the joint effect of BMSCs-seeded ANX grafting and G-CSF administration, and explore the relevant mechanisms. Adult SD rats were divided into five groups randomly: ANX group, ANX combined with G-CSF group, BMSCs-laden ANX group, BMSCs-laden ANX combined with G-CSF group, and autograft group. Eight weeks after transplantation, the detection of praxiology and neuroelectrophysiology was conducted, and then the morphology of the regenerated nerves was analyzed. The inflammatory response and apoptosis in the nerve grafts as well as the expression of the growth-promoting factors in the regenerated tissues were further assayed. G-CSF intervention and BMSCs implanting synergistically promoted peripheral nerve regeneration and functional recovery following ANX bridging, and the restoration effect was matchable with that of the autologous nerve grafting. Moreover, local inflammation was alleviated, the apoptosis of the seeded BMSCs was decreased, and the levels of the neuromodulatory factors were elevated. In conclusion, the union application of BMSCs-implanted ANX and G-CSF ameliorated the niche of neurotization and advanced nerve regeneration substantially. The strategy achieved the favorable effectiveness as an alternative to the autotransplantation. K E Y W O R D Sacellular nerve xenograft, bone marrow stromal cells, granulocyte colony-stimulating factor, peripheral nerve regeneration, transplantation

Simultaneous Regeneration of Bone and Nerves Through Materials and Architectural Design: Are We There Yet?

“…[97,99] Application of a BMSC-implanted scaffold containing granulocyte-colony stimulating factor and treatment with a low-frequency pulsed electromagnetic field ameliorated the niche of neurotization and improved nerve regeneration. [100,101] Exosomes derived from BMSCs influence innervation by preventing abnormal nerve invasion of the subchondral bone. [102] These exosomes have significant neuroprotective and neuritogenic effects on peripheral nerves, such as promoting the survival of retinal ganglion cells.…”

Combinatory transplantation of mesenchymal stem cells with flavonoid small molecule in acellular nerve graft promotes sciatic nerve regeneration

“…To determine whether 7, 8-DHF influenced the proliferation of BMSCs, four BMSC groups were seeded (1.25 × 10 3 cells/well) in 96-well plates with fresh culture medium for varying periods of time (1,2,4,6, and 8 days). The culture medium was changed daily.…”

“…The poor target reinnervation is primarily a result of too few regenerating axons, diminished trophic support and aberrant guidance of the axons that do regenerate. 1 , 2 Further complicating proper regeneration of peripheral axons is the degree of damage to the nerve and the need to repair or place a graft, often acellular nerve allografts (ANAs) to bridge a nerve gap in severe injuries. To aid in regeneration through ANAs, bone marrow stromal cell (BMSC) transplantation into the graft has been one promising approach to improve axonal regeneration and functional recovery.…”

Exploring miR‐21 as a key regulator in two distinct approaches of bone marrow stromal cells differentiation into Schwann‐like cells

“…Bone marrow stromal cells (BMSCs), derived from bone marrow, are adult stem cells with characteristics such as multipotent differentiation, easy sourcing, rapid in vitro proliferation, low immunogenicity, and the ability to secrete neurotrophic factors (NTFs). They have the potential to serve as ideal seed cells while overcoming ethical concerns (Chen et al, 2022;Jia et al, 2019). Dezawa et al used a composite factor induction method to induce rat BMSCs in vitro, resulting in their differentiation into SCLCs.…”