Clinical Study of NeuroRegen Scaffold Combined with Human Mesenchymal Stem Cells for the Repair of Chronic Complete Spinal Cord Injury

Abstract

Regeneration of damaged neurons and recovery of sensation and motor function after complete spinal cord injury (SCI) are challenging. We previously developed a collagen scaffold, NeuroRegen, to promote axonal growth along collagen fibers and inhibit glial scar formation after SCI. When functionalized with multiple biomolecules, this scaffold promoted neurological regeneration and functional recovery in animals with SCI. In this study, eight patients with chronic complete SCI were enrolled to examine the safety and efficacy of implanting NeuroRegen scaffold with human umbilical cord mesenchymal stem cells (hUCB-MSCs). Using intraoperative neurophysiological monitoring, we identified and surgically resected scar tissues to eliminate the inhibitory effect of glial scarring on nerve regeneration. We then implanted NeuroRegen scaffold loaded with hUCB-MSCs into the resection sites. No adverse events (infection, fever, headache, allergic reaction, shock, perioperative complications, aggravation of neurological status, or cancer) were observed during 1 year of follow-up. Primary efficacy outcomes, including expansion of sensation level and motor-evoked potential (MEP)-responsive area, increased finger activity, enhanced trunk stability, defecation sensation, and autonomic neural function recovery, were observed in some patients. Our findings suggest that combined application of NeuroRegen scaffold and hUCB-MSCs is safe and feasible for clinical therapy in patients with chronic SCI. Our study suggests that construction of a regenerative microenvironment using a scaffold-based strategy may be a possible future approach to SCI repair.

Injectable hydroxyphenyl derivative of hyaluronic acid hydrogel modified with RGD as scaffold for spinal cord injury repair

“…We used hWJ‐MSCs, as these cells represent an easily accessible source, with high potential for clinical applications. Moreover, a therapeutic benefit of hWJ‐MSCs in SCI alone as well as in combination with a biomaterial has been shown previously in several experimental and clinical studies …”

“…Moreover, a therapeutic benefit of hWJ-MSCs in SCI alone as well as in combination with a biomaterial has been shown previously in several experimental and clinical studies. [35][36][37]…”

Review of clinical neurorestorative strategies for spinal cord injury: Exploring history and latest progresses

“…reported NeuroRegen scaffold with human umbilical cord blood-mesenchymal stromal cells was effective in improving neurological functions for patients with chronic SCI [62]. This tissue engineering therapy did not fully clarify whether injured spinal tissue should be totally resected two months after injury and whether the procedure "totally resecting injured spinal cord tissue" is beneficial or harmful for SCI patients.…”

Holistic Approach to Axonal Regeneration in Cases of Spinal Cord Injury

“…The spinal cord contains myelin-sheathed neuronal tracts (including motor and sensory tracts), encased in white matter, which are responsible for afferent and efferent pathways [87,93]. These tracts guide nerve sprouting and stimulate the formation of nerve bundles, which may in-turn benefit axonal regeneration [88].…”