Stem cells, and specifically mesenchymal stem cells (MSCs), have long been considered as a promising therapeutic agent for the treatment of a wide variety of degenerative and ischemic diseases. Over this time, MSC immunomodulation, their capacity for multilineage differentiation, and their ability to self-renew have been well established and are now considered to be clinically relevant.
Considering this, scientists have hypothesized that the therapeutic application of MSCs in immune/inflammatory contexts may be more efficacious than other, more traditional approaches currently used in the field of regenerative medicine.
In this review, Wang et al. specifically focus on the non-traditional use of MSCs as a potential treatment towards immune/inflammatory-mediated diseases and identify important findings and trends in this area of study as they relate to specific immune/inflammation-mediated diseases, including graft-versus-host disease (GVHD), multiple sclerosis (MS), joint diseases [including Osteoarthritis (OA) and rheumatoid arthritis (RA)], inflammatory bowel disease (IBD), and inflammatory airway and pulmonary diseases.
While there have been several promising results indicated in a number of trials using MSC for treatment of GVHD, the same results have not consistently been observed in all trials. One potential reason for the observed difference in results could potentially be a result of heterogeneity observed in conducted trials. Significant observed differences included those between pediatric and adult patients, the type of stem cell transplanted, as well as the MSCs utilized. Interestingly, there has also been a significant difference between results of published trials occurring in Europe (generally positive) compared to those trials occurring in North America (more equivocal results). While MSCs have strong potential for use as a therapeutic agent for GVHD, additional study into patient population and stringent MSC processing criteria are required before consistent and reproducible results are able to be delivered.
As of the publication of this review (2016), Wang et al. identified 23 registered clinical trials using MSCs for the treatment of MS. Additionally, animal models exploring the use of MSCs for the treatment of MS have demonstrated strong therapeutic effects. While many of the clinical trials using MSCs for the treatment of MS were ongoing, several animal models and many additional preclinical studies demonstrated MSCs to have therapeutic efficacy for the treatment of patients with MS.
Since cartilage cannot regenerate, the use of MSCs in treatment of joint diseases are considered a strong therapeutic option for several of these conditions, including OA and RA. Considering that prevention of inflammation and immune attacks on joints must occur in order for the joint repair to occur, and considering the immunosuppressive properties associated with MSCs, MSCs are thought to be well suited for use in the treatment of OA – a thought that has been well supported in both small and large animal studies.
Additionally, several of the 38 clinical trials underway at publication of this review indicated positive results in reduction of OA-induced pain and other related symptoms and for joint repair as observed by cartilage regeneration. On the other hand, similar results have not been observed for RA. The authors point to the detailed mechanistic differences between RA and OA as the likely reason for the observed therapeutic differences observed between the two joint diseases.
The 19 clinical trials and several animal model studies have overwhelmingly demonstrated that MSC therapy is both safe and a highly viable therapeutic option for the treatment of IBD, especially CD fistula formations.
Considering that between 80-90% of MSCs delivered intravenously have been observed to rapidly reach the lungs, MSC therapy has been thought to be particularly well suited for treatment in several pulmonary diseases, including COPD, asthma,emphysema, and even pneumonia. However, while animal models and preclinical studies have demonstrated MSCs to be safe in this application, the 29 registered clinical studies using MSCs for pulmonary disorders have also indicated the application to be safe – but have yet to replicate the efficacy observed and reported in the previously mentioned preclinical animal studies.
The authors of the review conclude that hundreds of clinical trials evaluating the effectiveness of MSC therapy in this application have demonstrated their use to be safe. However, the overwhelmingly positive results reported in preclinical animal studies have not yet been observed through these clinical trials. Considering these findings, Wang et al. call for a better understanding on both the mechanistic properties of MSC Immunomodulation and the pathophysiological details and subsets with specific disease entities as a way to better tailor MSC therapy.
Source: “Human mesenchymal stem cells (MSCs) for treatment towards ….” 4 Nov. 2016, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095977/.
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