New Insights on Mesenchymal Stem Cells and Their Potential in Treating Aging and Diseases

A recent special issue published in the International Journal of Molecular Sciences provides a comprehensive overview of the significant role that mesenchymal stem cells (MSCs) and their derived products play in treating aging and various diseases. This issue explores the vast therapeutic potential of MSCs, offering new hope in addressing inflammation and degenerative diseases, which affect approximately 40% of the global population and often lack effective treatment options.

Despite the pharmaceutical industry's efforts in developing new drugs, with 55 new drugs introduced last year alone, the imbalance in tissue homeostasis remains a critical issue, leading to irreversible tissue damage, particularly exacerbated by an aging population. Traditional approaches targeting single diseases with single treatments are increasingly insufficient given the multifactorial nature of diseases and their complex pathologies. Hence, there is a growing interest in mimicking the natural tissue homeostasis mechanisms facilitated by MSCs under physiological conditions.

MSCs are known for their regenerative, anti-inflammatory, immunomodulatory, anti-oxidative stress, anti-fibrotic, anti-microbial, and anti-tumor properties. These effects are largely mediated through the secretion of cytokines and growth factors via a paracrine mechanism. Recently, the role of extracellular vesicles, particularly exosomes (nano-sized particles of 70-150 nanometers surrounded by a biologically active membrane), has been recognized in the field of regenerative medicine. When released by MSCs, these exosomes reproduce the biological effects of MSCs within the body's cell signaling pathways.

Interestingly, evidence now suggests a connection between MSC depletion and/or dysfunction and diseases such as lupus, rheumatoid arthritis, diabetes, psoriasis, and progeria syndrome. This finding indicates that MSC transplantation could positively impact the natural course of many diseases. Although intravenous MSC injections have shown good safety profiles, their widespread application faces several limitations. These include reduced cell half-life post-injection, potential cell senescence, embolism formation, risk of infection transmission, and various logistical and economic challenges.

To overcome these limitations, the development of acellular regenerative therapies using products derived from the secretome of MSCs has emerged as a strategic alternative. The high replication rate of MSCs facilitates these in vitro procedures. Moreover, bioreactor technology allows for the establishment of favorable culture conditions to produce and enhance MSC-derived secretome on a large scale. This new technological strategy not only avoids the drawbacks of cell-based MSC therapies but also offers additional advantages, such as better safety, dosage, and potency evaluation, easier storage, and ultimately a more cost-effective and practical clinical treatment method.

Furthermore, within the microvesicles constituting the MSC secretome, exosomes offer additional benefits, such as a longer half-life in blood, the ability to pre-load therapeutic products, the capacity to cross the blood-brain barrier, tropism for inflamed tissues and tumors, and the capability to deliver various bioactive substances to target tissues. These innovations introduce a new era of medicine with immense therapeutic potential, albeit with new challenges.

The challenges, opportunities, and goals for developing new drugs based on mesenchymal/medicinal signaling cells and their derived products include:

1. Selecting the appropriate type of MSC for each future application based on the biological characteristics of MSCs and the donor.
2. Producing and controlling the potency of their secretome-derived products in a controlled and repeatable manner.
3. Enhancing the quality of the MSC secretome through preconditioning techniques and/or genetic manipulation.
4. Combining these biological products with new biomaterials (e.g., thermally unstable hydrogels) for optimized tissue integration and/or biodistribution.
5. Utilizing MSC-derived extracellular vesicles as biological carriers of exosomes for drug delivery in cancer treatment and other therapies.
6. Exploring new and exciting clinical applications, such as treating brain diseases through intranasal administration of MSC-derived exosomes.
7. Strictly considering regulatory requirements.

The scientific knowledge about MSC biology and therapeutic potential, combined with appropriate technologies and supportive legal frameworks, paves the way for achieving these objectives. There is a pressing need among millions of patients, underscoring the importance of continued innovation and development in this field.