Decellularized peripheral nerve supports Schwann cell transplants and axon growth following spinal cord injury

Abstract

Schwann cell (SC) transplantation has been comprehensively studied as a strategy for spinal cord injury (SCI) repair. SCs are neuroprotective and promote axon regeneration and myelination. Nonetheless, substantial SC death occurs post-implantation, which limits therapeutic efficacy. The use of extracellular matrix (ECM)-derived matrices, such as Matrigel, supports transplanted SC survival and axon growth, resulting in improved motor function. Because appropriate matrices are needed for clinical translation, we test here the use of an acellular injectable peripheral nerve (iPN) matrix. Implantation of SCs in iPN into a contusion lesion did not alter immune cell infiltration compared to injury only controls. iPN implants were larger and contained twice as many SC-myelinated axons as Matrigel grafts. SC/iPN animals performed as well as the SC/Matrigel group in the BBB locomotor test, and made fewer errors on the grid walk at 4 weeks, equalizing at 8 weeks. The fact that this clinically relevant iPN matrix is immunologically tolerated and supports SC survival and axon growth within the graft offers a highly translational possibility for improving efficacy of SC treatment after SCI. To our knowledge, it is the first time that an injectable PN matrix is being evaluated to improve the efficacy of SC transplantation in SCI repair.

Hypoxia-Inducible Factor 1α (HIF-1α) Counteracts the Acute Death of Cells Transplanted into the Injured Spinal Cord

“…This result is similar to previous studies in which direct or indirect elevation of HIF-1 enhances transplant survival of cells transplanted into the damaged brain (Theus et al, 2008;Wu et al, 2010;Wakai et al, 2016), heart (Zhang et al, 2001), and pancreas (Stokes et al, 2013) . Although expression of HIF-1 protected the cells, the increase in transplant survival with HIF-1 was smaller than in previous spinal cord transplant studies targeting trophic support, anoikis, and/or cell death signaling (Golden et al, 2007;Hill et al, 2010;Patel et al, 2010;Lu et al, 2012;Robinson and Lu, 2017;Cerqueira et al, 2018). It is well-established that prolonged overexpression of HIF in transplanted cells induces tumor formation (Kung et al, 2000).…”

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

“…The main component of acellular nerves is the extracellular matrix (ECM) which constitutes the basilar membrane of Schwann cells. ECM exhibits complex grid‐like structure formed in the extracellular space and is composed of macromolecules such as secretory protein and polysaccharide, thus the basic framework for both of cell attachment and metabolism was maintained (Cerqueira et al, ; Gonzalez‐Perez, Udina, & Navarro, ). While preserving the endoneurial tubes, the cellular components, myelin sheath, and axons are absent in acellular nerves, thus the antigens which exist on the Schwann cell surface and the myelin sheath are removed and immunological rejection after transplantation is obviated.…”

Recent Advances on Magnetic Sensitive Hydrogels in Tissue Engineering

“…Cells, such as stem cells, neural cells, and osteoblasts, are an important component in tissue engineering (Cerqueira et al, 2018;He et al, 2018;Ahmad et al, 2019;Chen M. et al, 2019;Midgley et al, 2019); therefore, MNP labeled cells are becoming more and more available in magnetically bioinspired hydrogels. Henstock et al (2014) first added TREK1-MNPs or Arg-Gly-Asp (RGD)-MNPs into human mesenchymal stem cells (hMSCs) to fabricate MNP labeled cells, which were then seeded into either collagen hydrogels or poly(D, L-lactide-coglycolide) (PLGA) encapsulating bone morphogenetic protein-2 (BMP-2)releasing collagen hydrogels (as shown in Figure 2A).…”