The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection

Abstract

Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model.

Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury

“…Our observation from cytometry that PPN bridges placed in the site of injury both increase the number and support the axial orientation of regenerated axons emerging from both stumps agrees with previous studies reporting similar results from using cord hemisections treated in the acute stage, with PPN combined with other interventions (29,44). Functionally, treatment using only PPN promotes mild locomotor function recovery in both acute (45,46) and chronic stages (15). Similarly, the mild motor recovery observed here after single treatment with BMSCs in the chronic stage of injury agrees with the functional outcome after transplanting only BMSCs in the acute phase of injury (11,42,47).…”

“…The tubular structure and cells (mainly Schwann cells and macrophages) present in implants of PPN work as scaffolding and promote a permissive microenvironment for axonal regrowth in both acute and chronic spinal cord transection (25)(26)(27). Regenerated axons are able to cross both rostral and caudal graft-host interfaces (8,15,28,29).…”

“…Some successful combinations that promoted greater axonal regeneration than single treatments include treatments combining PPN + FGFα (41), PPN + ChABC (31), PPN + ChABC and PPN + BDNF (29), BMSCs + granulocytecolony stimulating factor (42), ChABC + NT3 (13), ChABC + rehabilitation (9), and PPN + BMSC (15).…”

“…If used independently, the benefits of the above-mentioned strategies seem insufficient to be translated to patients, but several experimental studies have shown that combined therapies may produce a greater benefit (11)(12)(13)(14). In fact, recently, we reported on the additive morphofunctional effect of combining PPN and BMSCs in a model of spinal cord transection (15). This justifies continuous testing for this kind of strategy.…”

Evaluación de ratas con lesión crónica de la médula espinal tratadas con una estrategia de combinación para mejorar el efecto restaurador de la inmunización con el péptido A91

“…Se centrifugó a 1500 rpm durante 5 min en PBS, las células se sembraron en placas de cultivo de 75cm2 y se utilizó el medio (Stem Cell Technologies, Vancouver, BC). Las células se mantuvieron en incubación a 37º C, con 5 % de CO2 y 95 % de humedad, se realizó cambio de medio cada tercer día (Buzoianu-Anguiano et al, 2015).…”