Comparison of Mesenchymal Stromal Cells Isolated from Murine Adipose Tissue and Bone Marrow in the Treatment of Spinal Cord Injury

Abstract

The use of mesenchymal stromal cell (MSC) transplantation to repair the injured spinal cord has shown consistent benefits in preclinical models. However, the low survival rate of grafted MSC is one of the most important problems. In the injured spinal cord, transplanted cells are exposed to hypoxic conditions and exposed to nutritional deficiency caused by poor vascular supply. Also, the transplanted MSCs face cytotoxic stressors that cause cell death. The aim of this study was to compare adipose-derived MSCs (AD-MSCs) and bone marrow-derived MSCs (BM-MSCs) isolated from individual C57BL6/J mice in relation to: (i) cellular characteristics, (ii) tolerance to hypoxia, oxidative stress and serum-free conditions, and (iii) cellular survival rates after transplantation. AD-MSCs and BM-MSCs exhibited a similar cell surface marker profile, but expressed different levels of growth factors and cytokines. To research their relative stress tolerance, both types of stromal cells were incubated at 20.5% O2 or 1.0% O2 for 7 days. Results showed that AD-MSCs were more proliferative with greater culture viability under these hypoxic conditions than BM-MSCs. The MSCs were also incubated under H2O2-induced oxidative stress and in serum-free culture medium to induce stress. AD-MSCs were better able to tolerate these stress conditions than BM-MSCs; similarly when transplanted into the spinal cord injury region in vivo, AD-MSCs demonstrated a higher survival rate post transplantation Furthermore, this increased AD-MSC survival post transplantation was associated with preservation of axons and enhanced vascularization, as delineated by increases in anti-gamma isotype of protein kinase C and CD31 immunoreactivity, compared with the BM-MSC transplanted group. Hence, our results indicate that AD-MSCs are an attractive alternative to BM-MSCs for the treatment of severe spinal cord injury. However, it should be noted that the motor function was equally improved following moderate spinal cord injury in both groups, but with no significant improvement seen unfortunately following severe spinal cord injury in either group.

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

“…What mediates the greater therapeutic effect of AD-MSCs in SCI compared to BM-MSCs or DP-MSCs remains to be fully understood. However, biological advantages in the proliferative capacity, cell viability under oxidative stress, secreted proteins, and immunomodulatory effects have been previously discussed for AD-MSCs and may be critical factors [23,76]. These data indicate that application of MSCs combined with fibrin matrix into the surface of spinal cord may be an effective and safe approach for delivering cells to the damaged area.…”

Efficacy of human HC016 cell transplants on neuroprotection and functional recovery in a rat model of acute spinal cord injury

“…Herein, bone marrow mesenchymal stem cells have been commonly considered as the first source of MSCs for SCI treatment. However, in the last years, several studies in animal models of SCI have demonstrated comparable results with AMSCs (Im, ; Kolar, Kingham, Novikova, Wiberg, & Novikov, ; Takahashi et al, ; Z. Zhou et al, ) which otherwise are much easier to isolate from healthy donors and in larger amounts than from bone marrow (Strioga, Viswanahatan, Darinskas, Slaby, & Michalek, ). These properties make of them a very attractive cell therapy alternative for SCI, as highlights the four clinical trials using these cells in subacute or chronic stages after SCI currently underway (Bajek et al, ).…”

“…Among cell therapies, mesenchymal stem cell (MSC) transplantation is an attractive and promising approach for treating SCI favoured by its excellent safety profile and efficacy potential, as extensively reported in preclinical models and clinical trials of acute, subacute, and chronic SCI (Dasari, Veeravalli, & Dinh, ; Qu & Zhang, ; Shende & Subedi, ; Vawda & Fehlings, ). In particular, adipose MSCs (AMSCs) are easily obtained and have excellent expansion capacities, as well as a unique immunomodulatory and paracrine competence able to modulate many of the detrimental effects elicited after acute SCI (Mazini, Rochette, Amine, & Malka, ; Menezes et al, ; Takahashi et al, ). These effects together with a proven preclinical efficacy and safety profile have paved the way for the clinical assessment of AMSCs in a variety of trials (Bajek et al, ; Hur et al, ; Jin et al, ).…”

Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis

“…The majority of grafted MSCs may not survive the first few days posttransplantation 22 . Thus, decreasing the expression of inflammation mediators may enhance MSC survival and improve their therapeutic efficacy 23,24 . In our study, LPS and FK506 were used to modulate the local immune microenvironment in neurotmesis.…”

“…MSCs can promote nerve regeneration after transplantation 1,18–20 . Unfortunately, the survival of transplanted MSCs is jeopardized by the unfavorable immune microenvironment of injured nerves, which substantially hampers the beneficial effect of MSCs on nerve repair 21–24 . It has been reported that the survival rate of MSCs can be increased by FK506 after spinal cord injury 14 .…”