Recovery of Function Following Grafting of Human Bone Marrow-Derived Stromal Cells into the Injured Spinal Cord

Abstract

This study evaluates functional recovery after transplanting human bone marrow-derived stromal cells (BMSCs) into contusion models of spinal cord injury (SCI). The authors used a high-throughput process to expand BMSCs and characterized them by flow cytometry, ELISA, and gene expression. They found that BMSCs secrete neurotrophic factors and cytokines with therapeutic potential for cell survival and axon growth. In adult immune-suppressed rats, mild, moderate, or severe contusions were generated using the MASCIS impactor. One week following injury, 0.5 to 1 x 106 BMSCs were injected into the lesioned spinal cord; control animals received vehicle injection. Biweekly behavioral tests included the Basso, Beattie, and Bresnahan Locomotor Rating Scale (BBB), exploratory rearing, grid walking, and thermal sensitivity. Animals receiving moderate contusions followed by BMSC grafts showed significant behavioral recovery in BBB and rearing tests when compared to controls. Animals receiving BMSC grafts after mild or severe contusion showed trends toward improved recovery. Immunocytochemistry identified numerous axons passing through the injury in animals with BMSC grafts but few in controls. BMSCS were detected at 2 weeks after transplantation; however, at 11 weeks very few grafted cells remained. The authors conclude that BMSCs show potential for repairing SCI. However, the use of carefully characterized BMSCs improved transplantation protocols ensuring BMSC, survival, and systematic motor and sensory behavioral testing to identify robust recovery is imperative for further improvement.

Intravenously transplanted bone marrow stromal cells promote recovery of lower urinary tract function in rats with complete spinal cord injury

“…In our study, BMSCs in the dorsal gray commissure, presenting proximal to both the sacral parasympathetic preganglionic neurons and the spinal EUS pattern generator, may promote the formation of the switch to coordinate bladder contraction and EUS relaxation by expressing neuronal and astroglial markers 18 or secreting neurotrophic factor and cytokine. 19 In the current study, we did not examine how these BMSCs differentiated after transplantation. Clearly, this is a limitation of the study.…”

The cell culture expansion of bone marrow stromal cells from humans with spinal cord injury: implications for future cell transplantation therapy

“…1 Somewhat surprisingly, MSCs have received considerable interest as possible donor cells in the development of cell transplantation therapies for spinal cord injury (SCI). [2][3][4][5][6][7] There are, however, a number of reasons for this. First and foremost, MSC transplantation has been demonstrated to enhance axonal regeneration and promote functional recovery in a variety of animal models of SCI.…”

“…First and foremost, MSC transplantation has been demonstrated to enhance axonal regeneration and promote functional recovery in a variety of animal models of SCI. [2][3][4][5][6][7] These studies have shown that transplanted MSCs integrate into host tissue following transplantation, supporting and remyelinating axons that traverse the injury site. MSCs also synthesize a number of growth factors that may contribute to tissue sparing and axonal regeneration, including nerve growth factor and brain-derived neurotrophic factor.…”

“…8 Importantly, though, MSCs represent an attractive donor source for various cell transplantation programmes, as they can be repeatedly isolated from bone marrow with relative ease, normally expanded into large numbers in vitro and reintroduced into patients as autografts, which prevents the need for immune rejection drugs in the clinical setting. 9 If donor cell number is a critical factor to the success of cell grafting for SCI treatment, as is likely to be the case, then it is important to note that the typical injury in rodent models of SCI is only a few millimetres in length, [2][3][4][5][6][7] whereas the length of lesions in humans can reach several centimetres. Recently, using an in vitro model, we have shown that human MSCs promote nerve growth over inhibitory molecules present at the lesion site in SCI; furthermore, the number of nerves that were subsequently able to grow over these molecules was related to the number of MSCs present.…”

Effects of plating density and culture time on bone marrow stromal cell characteristics

“…Because MSC can be easily obtained using a simple bone marrow aspiration and show an extensive capacity for expansion in vitro, these cells have been considered as candidates for cell therapy. So far, MSC have been used with varying success to improve neurological (7)(8)(9), cardiovascular (10), blood-related (11,12) and musculoskeletal disorders (13,14).…”