Protective effects of bone marrow stromal cell transplantation in injured rodent brain: Synthesis of neurotrophic factors

Abstract

Several groups have suggested that transplantation of marrow stromal cells (MSCs) promotes functional recovery in animal models of brain trauma. Recent studies indicate that tissue replacement by this method may not be the main source of therapeutic benefit, as transplanted MSCs have only limited ability to replace injured central nervous system (CNS) tissue. To gain insight into the mechanisms responsible for such effects, we systematically investigated the therapeutic potential of MSCs for treatment of brain injury. Using in vitro studies, we detected the synthesis of various growth factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT-3). Enzyme-linked immunosorbent assay (ELISA) demonstrated that MSCs cultured in Dulbecco's modified Eagle medium (DMEM) produced substantial amounts of NGF for at least 7 weeks, whereas the levels of BDNF, GDNF and NT-3 remained unchanged. In studies in mice, after intraventricular injection of MSCs, NGF levels were increased significantly in cerebrospinal fluid by ELISA, confirming our cell culture results. Further studies showed that treatment of traumatic brain injury with MSCs could attenuate the loss of cholinergic neuronal immunostaining in the medial septum of mice. These studies demonstrate for the first time that by increasing the brain concentration of NGF, intraventricularly transplanted MSCs might play an important role in the treatment of traumatic brain injury.

Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury

“…43 The potentially important role of induction of local neurotrophic factors is also supported by Chen et al, 44 who showed that intraventricular injection of MSCs in a murine model resulted in an increase in NGF levels as measured in the cerebrospinal fluid. Other mechanisms have been suggested to explain the action of transplanted MSCs, such as an elevated level of transforming growth factor-b (TGF-b) that helps to reduce the formation of scar tissue, and restoration of cerebral blood flow and the blood-brain barrier in models of traumatic brain injury 45 and stroke.…”

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

“…injury [165,[169][170][171][172] and potentially in clinical settings [173,174]. However, previous studies show that only a small proportion of transplanted MSCs actually survive and few MSCs differentiate into neural cells in injured brain tissues.…”

Current and future medical therapeutic strategies for the functional repair of spinal cord injury

“…BMCs grafting on SCI injury models have been studied and it has been observed that the transplanted BMCs improve neurological deficits by generating myelin producing cells or neural cells [117,118] . Furthermore, BMCs can produce neuroprotective cytokines, rescuing the neurons with impending cell death in case of injury [119,120] . Also, several clinical trials have explored the hypothesis that cell transplantation may enhance the recovery of neurological functions after SCI.…”