Neural stem/progenitor cell‐laden microfibers promote transplant survival in a mouse transected spinal cord injury model

Abstract

Previous studies have demonstrated that transplantation of neural stem/progenitor cells (NS/PCs) into the lesioned spinal cord can promote functional recovery following incomplete spinal cord injury (SCI) in animal models. However, this strategy is insufficient following complete SCI because of the gap at the lesion epicenter. To obtain functional recovery in a mouse model of complete SCI, this study uses a novel collagen-based microfiber as a scaffold for engrafted NS/PCs. We hypothesized that the NS/PC-microfiber combination would facilitate lesion closure as well as transplant survival in the transected spinal cord. NS/PCs were seeded inside the novel microfibers, where they maintained their capacity to differentiate and proliferate. After transplantation, the stumps of the transected spinal cord were successfully bridged by the NS/PC-laden microfibers. Moreover, the transplanted cells migrated into the host spinal cord and differentiated into three neural lineages (astrocytes, neurons, and oligodendrocytes). However, the NS/PC-laden scaffold could not achieve a neural connection between the rostral end of the injury and the intact caudal area of the spinal cord, nor could it achieve recovery of motor function. To obtain optimal functional recovery, a microfiber design with a modified composition may be useful. Furthermore, combinatorial therapy with rehabilitation and/or medications should also be considered for practical success of biomaterial/cell transplantation-based approaches to regenerative medicine.

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair

“…NSPCs are capable of differentiating into three main CNS cell types: neurons, astrocytes, and oligodendrocytes. Readers are referred to an extensive review of preclinical transplantation studies for spinal cord regeneration [57,[60][61][62]. However, there are numerous challenges ahead before cell therapy can be translated into a clinical testing.…”

A novel composite type I collagen scaffold with micropatterned porosity regulates the entrance of phagocytes in a severe model of spinal cord injury

“…Besides the absence of spontaneous recovery in untreated animals, some authors failed to observe functional motor recovery in injured rodents treated with scaffold-based strategy. 28,36,37 In all abovementioned studies a segment resection model was utilized. It was suggested that the absence of recovery of hindlimbs function in animals subjected to complete spinal cord transection was likely due to insufficient axon regeneration and integration in functional circuit.…”

Rod‐Shaped Neural Units for Aligned 3D Neural Network Connection

“…[22,23,37,38] We used three types of neural cells to fabricate microfiber-shaped neural tissues: primary mouse neural stem cells (mNSCs) dissected from the midbrain of mice (mNSC units), primary cortical cells (cortical units), and primary hippocampal cells (hippocampal units). To prepare the rod-shaped neural units in an accurate and reproducible manner, we developed a fiber-cutting device that can fix the microfiber-shaped neural tissues in a culture In the brain, 3D neural networks such as the hippocampalprefrontal pathway, [1,2] amygdala pathway, [3][4][5] and visual pathway [3,6,7] comprise various independent regions that are connected by aligned nerve fibers.…”