Therapeutic Efficacy of Mesenchymal Stem Cells and Mesenchymal Stem Cells-derived Neural Progenitors in Experimental Autoimmune Encephalomyelitis

Abstract

Background and ObjectivesThe goal of treatment for MS is to reduce the inflammation and induce the regeneration of degenerated axons. Considering the anti-inflammatory and regenerative capacity of mesenchymal stem cell (MSCs), in this study the therapeutic efficacy of allogeneic MSCs and MSCs-derived neural progenitor cells (MSCs-NPs) was investigated in cellular therapy of chronic experimental autoimmune encephalomyelitis (EAE).Methods and ResultsMSCs, MSCs-NPs and MSCs+MSCs-NP were administered intravenously to EAE mice on days 22, 29, and 36 post immunization. The levels of cytokines and PGE2 in sera or supernatant of in vitro cultured splenocytes derived from treated mice were measured by ELISA. The results of this study showed that in comparison to MSCs monotherapy, MSCs-NPs administration had a more profound capability of inhibiting the proliferation of pathogenic MOG35–55-specific T cells, decreasing IFN-γ production and increasing anti-inflammatory IL-10 cytokine production. These findings could be explained by higher ability of in vitro cultured MSCs-NPs in production of PGE2 compared to MSCs. In line with these findings, while the administration of MSCs and MSCs-NPs significantly decreased the clinical scores of EAE in comparison with the untreated EAE group, MSCs-NPs were significantly more efficient in reducing clinical score compared to MSCs. Of interest, combined therapy with MSCs and MSCs-NPs did not provide any benefit over monotherapy with MSCs-NPs.ConclusionsIn comparison to MSCs, allogenic MSCs-NPs are more potent in the attenuation of EAE.

Mesenchymal stem cells: Cell therapy and regeneration potential

“…Stem cell‐based therapies can greatly impact the field of regenerative medicine. MSCs have been used in preclinical and clinical studies to treat degenerative diseases, such as AD (Cui et al, ; Han et al, ; J. Shin et al, ; X. Wang, Ma, et al, ), DDD (Ahn et al, ; Beeravolu et al, ; Pereira et al, ; Perez‐Cruet et al, ), MS (Harris et al, ; Nasri et al, ; Planchon et al, ), PD (Jamali et al, ; H. Kim, Lee, et al, ), and RDD (Mead, Amaral, & Tomarev, ), as summarized in Table . The regenerative mechanisms of transplanted MSCs for these diseases are still unclear; however, some reports have suggested that MSCs have the potential to differentiate or have paracrine effects in vivo (Lee, Choi, Cha, & Hwang, ).…”

“…These dopaminergic neuron cells survived when transplanted into a rat model of PD and displayed greater improvement of behavioral impairments (Y. Wang et al, ). In addition, MSCs have been investigated for the treatment of MS (Harris et al, ; Nasri et al, ; Planchon et al, ). Potential of the MSCs differentiated into neural progenitor cells was investigated to treat MS using a chronic experimental autoimmune encephalomyelitis (EAE) mouse model (Constantinescu, Farooqi, O'Brien, & Gran, ).…”

“…MSCs have shown promising outcomes in preclinical and clinical studies for treating pain and degenerative diseases such as AD, DDD, MS, PD, and RDD and providing immunomodulatory, neuroprotective, and anti‐inflammatory responses in vivo (Beeravolu et al, ; Ding, Kumar, & Mok, ; Gugliandolo, Bramanti, & Mazzon, ; Nasri et al, ; Osborne, Sanderson, & Martin, ; Perez‐Cruet et al, ; Turgeman, ; van Buul et al, ; R. Zhang, Liu, et al, ). Studies have shown that MSCs can be differentiated to NPCs to regenerate the NP in the IVD and to retinal progenitor cells to regenerate the retina within the eye (Beeravolu et al, ; Ding et al, ; Perez‐Cruet et al, ).…”

“…MSCs have been used in preclinical and clinical studies to treat degenerative diseases, such as AD (Cui et al, 2017;Han et al, 2018;X. Wang, Ma, et al, 2018), DDD (Ahn et al, 2015;Beeravolu et al, 2018;Pereira et al, 2016;Perez-Cruet et al, 2018), MS (Harris et al, 2018;Nasri et al, 2018;Planchon et al, 2018), PD (Jamali et al, 2018;H. Kim, Lee, et al, 2018), and RDD (Mead, Amaral, & Tomarev, 2018), as summarized in Table 2.…”

“…Wang, Ma, et al, 2018) Bone and cartilage diseases (Jo et al, 2014;Kastrinaki et al, 2013) Autoimmune diseases (Xu, 2018;W. Zhang, Feng, et al, 2018) Amyotrophic lateral sclerosis (Bonafede & Mariotti, 2017) Diabetes (Evangelista et al, 2018;Gabr et al, 2018) Glaucoma (Manuguerra-Gagne et al, 2013;Osborne, Sanderson, & Martin, 2018;Roubeix et al, 2015) Graft vs host disease (Jurado et al, 2017;Zhao et al, 2015) Intervertebral disc disease (Ahn et al, 2015;Beeravolu et al, 2018;Pereira et al, 2016;Perez-Cruet et al, 2018) Multiple sclerosis (Harris et al, 2018;Nasri et al, 2018;Planchon et al, 2018) Myocardial infarction ( investigated for the treatment of chronic tissue ulcers caused by diabetes. Patients were administered with MSCs for skin healing showed an improvement in microvascularisation structure (Kirana et al, 2012).…”