Effects of Intrathecal Injection of the Conditioned Medium from Bone Marrow Stromal Cells on Spinal Cord Injury in Rats

Abstract

Bone marrow stromal cells (BMSCs) have been studied for the treatment of spinal cord injury (SCI). In previous studies, we showed that the transplantation of BMSCs, even though they disappeared from the host spinal cord within 1-3 weeks after transplantation, improved locomotor behaviors and promoted axonal regeneration. This result led to the hypothesis that BMSCs might release some neurotrophic factors effective for the treatment of SCI. The present study examined this by injecting the conditioned medium (CM) of BMSCs to treat SCI in rats. The spinal cord was contusion-injured, followed immediately by continuous injection for 2 weeks of the CM of BMSCs through the cerebrospinal fluid via the 4th ventricle using an Alzet osmotic pump. Locomotor behaviors evaluated by the Basso-Beattie-Bresnahan score were markedly improved in the CM-injection group, compared with the control group, at 1 to 4 weeks post-injection. The contusion-injured site of the spinal cord was identified as an astrocyte-devoid area, which contained no astrocytes but was filled with collagen matrices and empty cavities of various sizes. Collagen matrices contained type I collagen and laminin. Numerous axons extended through the collagen matrices of the astrocyte-devoid area. Axons were surrounded by Schwann cells, exhibiting the same morphological characteristics as peripheral nerve fibers. The density of axons extending through the astrocyte-devoid area was higher in the CM-injection group, compared with the control group. CM injection had beneficial effects on locomotor improvements and tissue repair, including axonal regeneration, meaning that the BMSC-CM stimulated the intrinsic ability of the spinal cord to regenerate. Activation of the intrinsic ability of the spinal cord to regenerate by the injection of neurotrophic factors such as BMSC-CM is considered to be a safe and preferable method for the clinical treatment of SCI.

The Therapeutic Potential of Conditioned Medium from Human Breast Milk Stem Cells in Treating Spinal Cord Injury

“…Loss of differentiation potential, initiation of the host immune response, difficulties in delivery, and poor engraftment of transplanted cells are the major limitations of cell-based therapies [8,24]. Since the main effects of MSCs are likely mediated by paracrine mechanisms [25], we examined the effect of BMSC-CM as an alternative treatment for SCI. These experiments demonstrated that BMSC-CM can protect neuronal cells [26,27].…”

Regenerative Therapies for Spinal Cord Injury

“…Cell-based therapy may be suitable for the treatment of discrete lesions in SCI (Figs. 3 and 5) to provide the following: (1) trophic support, 59 (2) immunomodulation, 60,61 (3) angiogenesis, 35 (4) and generation of new CNS cells, 1,6 which may form functional relays (Fig. 6).…”

“…70 Intrathecal injection of conditioned medium of MSCs into experimental SCI in rats was found to increase axonal regeneration and improve locomotor recovery 1-4 weeks after the treatment. 59 Stem cell-conditioned media contain several potentially regenerative factors, including insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), transforming growth factor b1 (TGF-b1), and HGF. It has been reported that the use of such media are more effective than using individual factors or their combinations in enhancing the survival of neurons and growth of neurites.…”

Conditioned medium of mesenchymal stem cells delays osteoarthritis progression in a rat model by protecting subchondral bone, maintaining matrix homeostasis, and enhancing autophagy

“…Considering all these secretions are contained in MSCs' culture medium, also known as conditioned medium (CM; Soleimanifar et al, 2018), it is a safer choice to use cell-free CM as a substitute for MSCT. Increasing publications have demonstrated the effectiveness of cell-free CM in ameliorating high glucose-induced degradation of ECM (Qi et al, 2018), inflammatory arthritis (Kay et al, 2017), wound healing (Amini et al, 2018), and spinal cord injury (Kanekiyo et al, 2018). Considering the regenerative property of CM, we therefore measured the potential of CM against OA in a rat model.…”