Rapid advancements in biomedical research have underscored the need for new drug discovery tools that offer a transformative pathway to expedite the identification and development of novel therapeutic interventions. Mesenchymal Stem Cells (MSCs; also known as Mesenchymal Stromal Cells) provide researchers with a crucial tool they need to revolutionize therapeutic development.
In regenerative medicine, MSCs are remarkable for their ability to differentiate into bone, cartilage, muscle, and adipose cells, making them valuable for both basic research and therapeutic applications. This versatility extends to drug studies, where MSCs provide insights into drug effects on various cell types. Their regenerative potential holds promise for treating a wide range of medical conditions, from bone defects to neurodegenerative diseases. MSC differentiation studies aid in identifying drug targets and understanding drug effectiveness and safety, shaping the future of pharmaceutical innovation.
MSCs can originate from multiple sources. Primary MSCs are derived directly from sources such as bone marrow or adipose tissue. Induced pluripotent stem cell (iPSC)-derived MSCs are generated by reprogramming adult cells, like skin or blood cells, into a pluripotent state and then directing them to become MSCs. Each source has its advantages: primary MSCs have been extensively studied and used in therapies, while iPSC-MSCs offer the ability to create cell line banks with minimal lot-to-lot variability while retaining the potential to differentiate into all three MSC lineages (adipocytes, chondrocytes, and osteocytes).
In addition to MSCs themselves, many researchers are investigating the uses of subcellular fractions of mesenchymal cells, such as exosomes or the secretome. Exomes are vesicles containing a variety of factors that are shed by the MSCs under appropriate conditions. They are under active investigation for several therapeutic applications.1 The secretome is the collection of all material secreted by the cells, including exosomes. These fractions are rich in immunomodulatory factors, making them ideal therapeutic agents in a wide variety of areas.
Mesenchymal Stem Cells offer a promising avenue for disease modelling and therapy development. One area of focus is on neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. In the case of Alzheimer's and Parkinson's diseases, exosomes and the secretome are increasingly used as therapeutic agents2 to modulate degeneration and promote healing. iPSC- derived MSC lines generated from patients provide an opportunity to create personalized consistent in vitro models without the concern of exhausting the cell bank.
One area where MSC-based disease modelling is proving promising is research into treating bone and cartilage diseases. Mucopolysaccharidosis IVA (Morquio syndrome A) is a lysosomal disease that causes skeletal dysplasia. iPSC-derived MSCs were used to develop a chondrocyte-based model to test possible therapies.3 Acquired tracheomalacia (ATM) is characterized by a loss of strength in the tracheal structure, resulting in difficulty breathing and other complications. In a sheep study,4 MSC-derived chondrocytes were used to develop a tissue engineered implant which resulted in improvement in function.
Uses for these adult stem cells extend beyond regeneration. Unlike some immune cells that can trigger inflammation, MSCs act as moderators. They can suppress excessive immune responses and promote tissue repair. This immunomodulatory prowess makes them ideal for studying and developing drugs for immune-related disorders and conditions characterized by inflammation, such as autoimmune diseases5 or graft-versus-host disease (GVHD).6
Furthermore, MSCs boast a low immunogenicity profile, mitigating the risk of immune rejection and facilitating allogeneic7 transplantation without the need for stringent matching criteria. This remarkable feature underscores the potential of MSC-based therapies for off-the-shelf availability, expediting treatment delivery and broadening accessibility to patients in need.
MSCs are active participants in the healing process.8 For example, a number of studies9 have examined the utility of MSCs and exosomes from them as aids in skin wound healing. MSCs secrete a rich cocktail of bioactive molecules, including growth factors, cytokines, and extracellular vesicles. These paracrine factors play a crucial role in tissue repair and regeneration by influencing the behavior of neighboring cells and tissues. Understanding these factors can aid in the development of drugs that mimic or enhance their beneficial effects.
Rapid advancements in biomedical research have emphasized the necessity for innovative drug discovery tools, and MSCs are emerging as a pivotal resource. Their remarkable ability to differentiate into various cell types makes them invaluable in regenerative medicine and drug studies, offering insights into drug effects and aiding in identifying targets. Derived from sources like bone marrow or generated through reprogramming adult cells, MSCs exhibit versatility and promise treating conditions ranging from bone defects to neurodegenerative diseases to tissue repair. Moreover, subcellular fractions of MSCs, such as exosomes and the secretome, are actively investigated for therapeutic applications due to their immunomodulatory properties. Because of their beneficial properties, MSCs are reshaping the landscape of pharmaceutical innovation and therapeutic development.
REPROCELL can help your MSC-based clinical, research, or gene editing projects!
Streamline your MSC research with REPROCELL's extensive portfolio of convenient, ready-to-ship products. From primary MSC, MSC lines derived from iPSCs to specialized media and culture reagents. We provide researchers with the tools they need to unlock the full potential of MSCs in their quest for drug discovery.
REPROCELL can also help with your clinical MSC project by providing both off-the-shelf and custom GMP MSCs and MSC Master Cell Banks, including cell-free MSC-derived secretome and exosome cell therapies. Our expertise extends beyond the realms of basic research, encompassing a comprehensive understanding of disease modelling, drug testing, and regenerative medicine applications. By pushing the boundaries of science, we develop innovative tools for cell therapy and drug discovery, offering a path towards revolutionizing healthcare outcomes.
References
- Lofty, AboQuella & Wang. Mesenchymal Stromal/Stem Sell (MSC)-Derived Exosomes in Clinical Trials. Stem Cell Res Ther 14, 66 (2023).
- Ghasemi et al. Mesenchymal Stromal Cell-Derived Secretome-Based Therapy for Neurodegenerative Diseases: Overview of Clinical Trials. Stem Cell Res Ther 14, 122 (2023). Sierra. Development of a Cellular Model for Morquio A Syndrome. 2013.
- Melgarejo-Ramirez et al. Novel Therapy for Acquired Tracheomalacia with a Tissue-Engineered Extraluminal Tracheal Splint and Autologous Mesenchymal-Derived Chondrocytes. Int Arch Otorhinolaryngol 27(02), (2023).
- Zaripova et al. Mesenchymal Stem Cells in the Pathogenesis and Therapy of Autoimmune and Autoinflammatory Diseases. Int. J. Mol. Sci. 24 (2023).
- Kelly & Rasko. Mesenchymal Stromal Cells for the Treatment of Graft Versus Host Disease. Front Immunol 12 (2021).
- Li, Zhao, Cheng & Weng. Allogenic vs. Autologous Mesenchymal Stem/Stromal Cells in their Medication Practice. Cell Biosci 11, 187 (2021).
- Bagno, Salerno, Balkan & Hare. Mechanism of Action of Mesenchymal Stem Cells (MSCs): Impact of Delivery Method. Expert Opin Biol Ther 22, 4 (2022).
- Saadh et al. Advances in Mesenchymal Stem/Stromal Cell-Based Therapy and their Extracurricular vesicles for Skin and Wound Healing. Human Cell 36, (2023).