Fight Aging!

Arguably the most robust and reliable of currently available stem cell therapies, though still varying widely in outcome between sources of cell, methods of delivery, and patients, judging by the studies conducted to date, are those involving mesenchymal stem cells. They are now widely used for all sorts of musculoskeletal and joint issues that might benefit from less inflammation and more regeneration. The transplanted cells typically don't live for long, but they do generate signals that produce a sizable temporary change in the local environment, including suppression of chronic inflammation.

It is an interesting question as to the degree to which the observed results of modestly enhanced regeneration following mesenchymal stem cell therapy are secondary to reduced inflammation, versus being caused by pro-regenerative signaling that doesn't relate to inflammation. It is becoming clear that chronic inflammation degrades the normal processes of regeneration and tissue maintenance, all of which involve an intricate dance of stem cells, immune cells, and various other cell populations specific to each tissue type. When immune cell behavior is running off the rails because of constant inflammatory signaling, regeneration is diminished.

Here, I'll point out a small open access study on the use of mesenchymal stem cell therapy for the common age-related joint issue of osteoarthritis, in which cartilage and bone break down. It differs from most earlier studies in tracking patient outcomes for a longer period of time following the procedure, something that is probably needed in order to provide a more definitive answer as to which of the various methodologies of treatment are effective. Osteoarthritis is an inflammatory condition, though the inflammation is localized to the problem joints. Given the results from recent studies, it is beginning to look likely that senescent cells are the major cause of this condition. Since these errant cells are known to generate a potent mix of inflammatory signaling, this all fits together quite nicely.

Mesenchymal stem cell therapies don't address the cause of the issue, but they do appear to damp down inflammation and perhaps issue other regenerative signals for long enough to allow tissues to accomplish some repair of the structural damage despite the presence of senescent cells. It will be interesting to see how senolytic therapies to remove senescent cells compare, as that should provide a good answer to the question above regarding the split of benefits between reduced inflammation versus increased regenerative signaling.

Intra-articular injection of expanded autologous bone marrow mesenchymal cells in moderate and severe knee osteoarthritis is safe: a phase I/II study

Knee osteoarthritis (KOA) is a common condition affecting the adult population causing pain and dysfunction of the knee joint. Subsequently, there is a negative impact on the quality of life of these patients. A recent meta-analysis of the 11 trials with 558 patients using mesenchymal stem cells (MSCs) was published. There was an improvement in various clinical scores. The authors concluded that there was no significant difference in the comprehensive evaluation index after stem cell treatment, despite the significant improvement in clinical symptoms and cartilage morphology. A recent phase I-II of expanded autologous bone marrow stem cells has been published. It reported the safety and effectiveness of this modality. There is one published work using allogeneic bone marrow-derived MSCs in advanced KOA in humans showing clinical improvement but no significant MRI improvement.

In this paper, we report on the results of 13 patients who were treated by expanded autologous bone marrow mesenchymal stem cells (BM-MSCs) in an open-label phase I prospective study and followed for 2 years for any adverse events and for efficacy by normalized Knee Osteoarthritis Outcome Score (KOOS) and by MRI.

Knee cartilage has limited regenerative capacity. Mesenchymal stem cells (MSCs) are known to have paracrine and differentiation properties. They can produce extracellular matrix within the joint. These properties make them good target for use in the regeneration of knee cartilage. Whether MSCs stimulate the proliferation and differentiation of resident progenitor cells or they differentiate into chondrocytes remains to be clarified. Rabbit and goat models of osteoarthrosis suggest that the repair occurs through paracrine effects by stimulation of endogenous repair mechanisms.

This work shows that the use of BM-MSCs is safe with only minimal early pain in some patients in the injected joint which resolved quickly without any intermediate or long-term clinical or biochemical adverse events. Bone marrow is attractive since it can easily be harvested as an outpatient procedure and without the need for patient hospitalization. Patients were followed up for 2 years. The work provides preliminary evidence that BM-MSCs are effective in KOA, as judged by the significant improvement in KOOS and by MRI. Mean knee cartilage thickness measured by MRI improved significantly. All symptoms significantly improved conferring significant improvement in the quality of life of these patients with grade II and III KOA. However, we wish to emphasize that the small number of participants in this study prohibits generalization of efficacy, and further work is warranted.

We suggest that next trials should also explore the dose of MSC and the source of MSC. There is a need to establish the safety of allogeneic MSC for KOA. The use of allogenic MSC can be standardized and the dose can be better controlled, and the cell variability can be reduced to the minimum. We believe that MSCs are potential definitive therapy for KOA.