What is MSC-CM and how does it work?

Regenerative medicine based on stem cells is currently the center of attention. Stem cells lead the way in new therapies because they can self-renew and differentiate into various cell lines. Stem cells primarily include embryonic and somatic stem cells [1]. Somatic stem cells comprise hematopoietic stem cells and mesenchymal stem cells (MSCs). MSCs can adhere when maintained in suitable culture conditions. They can differentiate into bone, fat, and cartilage cells [2]. Several studies have demonstrated the significant potential of MSCs in tissue regeneration.

However, stem cell-based therapies have certain limitations, such as inconsistent quality control processes in large-scale cell production, reduced effectiveness in regeneration after multiple proliferations, and the requirement for highly specialized techniques and high treatment costs. Moreover, there are inherent risks associated with stem cell therapies, such as immune reactions and infectious diseases [3-5]. Therefore, the effectiveness of stem cell therapies may not always meet clinical treatment requirements. Stem cells in a diseased body environment experience impaired self-renewal and differentiation ability, leading to tissue regeneration that does not meet the desired requirements. A better alternative to directly using stem cells for tissue regeneration while eliminating associated risks is the utilization of products secreted by stem cells into the culture environment (mesenchymal stem cell-conditioned medium: MSC-CM) [2,6].

The factors secreted by cells under these conditions are classified as cytokines, chemokines, cell adhesion molecules, lipid intermediates, growth factors, exosomes, microvesicle, etc. [7]. MSC-CM can play a significant role in tissue repair and regeneration. As a cell-free technique, MSC-CM is more convenient and safer than direct MSC transplantation. In addition, MSC-CM utilizes proteins and other components instead of whole cells to prevent host immune reactions, can be stored for a relatively long time without the use of harmful cryopreservations like DMSO, and has been cost-effective [8]. Hence, utilizing MSC-CM could be an efficient method for tissue regeneration.

Preparation of MSC CM for transplantation procedure

Effects of MSC-CM

MSC-CM enhances vascular formation by promoting cell mobility and proliferation. Additionally, its immune-modulating potential can be utilized for tissue regeneration [9]. According to reports, MSC-CM modulates increased TGF-β and simultaneously regulates decreased IL-17 in the treatment of colitis [10]. Furthermore, MSC-CM can be a safe and easily applicable alternative therapy for specific conditions, like hair restoration and skin rejuvenation, with promising outcomes. It can also be an effective treatment for scar reduction and improvement of psoriasis [11,12].

One of the strongest effects of MSC CM is blood vessel proliferation, therefore, besides stem cells, MSC CM is used with stem cells to support the treatment of diabetes, kidney failure, and disorders. metabolism…

The properties of MSC-CM vary depending on the cell source. Another crucial aspect is the time of CM collection from cells and the concentration steps required to obtain CM. The same type of cells has been reported to release varying levels of secretory factors depending on the culture conditions and scaffolds. Studies have published the application of MSC-CM in treating injuries and diseases in various organs, such as acute kidney injury, myocardial infarction, liver failure, lung diseases, and nerve injuries, where MSC-CM significantly promoted the repair and regeneration of damaged tissues and/or organs [13]. Researchers have proven the effectiveness of MSC-CM in conditions like stroke, Alzheimer’s disease, acute kidney injury, rheumatoid arthritis, diabetes, and other diseases, as well as in conditions affecting bone tissue, such as fractures and non-union bone defects [2,14].

Future potential of MSC-CM

The role of stem cells in promoting tissue regeneration primarily depends on their secretion functions and molecules. Using MSC-CM is safe and effective for tissue regeneration. Researchers can adjust MSC-CM as needed by using different stimulating compounds or varying culture conditions during the in vitro culture of MSCs. By using different stimulating compounds or varying culture conditions during the in vitro culture of MSCs, researchers can optimize the concentration of effective components and growth factors in MSC-CM as needed. Based on their potential and functionality, tissue regeneration through MSC-CM holds significant promise in treating various multifaceted diseases.

References:

1. Chen, Fa-Ming, and Yan Jin. “Periodontal tissue engineering and regeneration: current approaches and expanding opportunities.” Tissue Engineering Part B: Reviews16, no. 2 (2010): 219-255.
2. Kim, Young Guk, Jonghoon Choi, and Kyobum Kim. “Mesenchymal Stem Cell‐Derived Exosomes for Effective Cartilage Tissue Repair and Treatment of Osteoarthritis.” Biotechnology journal15, no. 12 (2020): 2000082.
3. Caplan, Henry, Scott D. Olson, Akshita Kumar, Mitchell George, Karthik S. Prabhakara, Pamela Wenzel, Supinder Bedi et al. “Mesenchymal stromal cell therapeutic delivery: translational challenges to clinical application.” Frontiers in immunology10 (2019): 1645.
4. Bogatcheva, N. V., and M. E. Coleman. “Conditioned medium of mesenchymal stromal cells: a new class of therapeutics.” Biochemistry (Moscow)84 (2019): 1375-1389.
5. Yang, Chih-Yu, Pu-Yuan Chang, Jun-Yi Chen, Bo-Sheng Wu, An-Hang Yang, and Oscar Kuang-Sheng Lee. “Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6.” Stem Cell Research & Therapy12 (2021): 1-12.
6. Li, Yu, Xin Gao, and Jinbing Wang. “Human adipose‑derived mesenchymal stem cell‑conditioned media suppresses inflammatory bone loss in a lipopolysaccharide‑induced murine model.” Experimental and therapeutic medicine15, no. 2 (2018): 1839-1846.
7. Kumar, Praveen, Sangeetha Kandoi, Ranjita Misra, S. Vijayalakshmi, K. Rajagopal, and Rama Shanker Verma. “The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine.” Cytokine & growth factor reviews46 (2019): 1-9.
8. Kovach, Tracy K., Abhijit S. Dighe, Peter I. Lobo, and Quanjun Cui. “Interactions between MSCs and immune cells: implications for bone healing.” Journal of immunology research2015 (2015).
9. Katagiri, Wataru, Masashi Osugi, Kazuhiko Kinoshita, and Hideharu Hibi. “Conditioned medium from mesenchymal stem cells enhances early bone regeneration after maxillary sinus floor elevation in rabbits.” Implant dentistry24, no. 6 (2015): 657-663.
10. Heidari, Maryam, Sedigheh Pouya, Kaveh Baghaei, Hamid Asadzadeh Aghdaei, Saeed Namaki, Mohammad Reza Zali, and Seyed Mahmoud Hashemi. “The immunomodulatory effects of adipose‐derived mesenchymal stem cells and mesenchymal stem cells‐conditioned medium in chronic colitis.” Journal of Cellular Physiology233, no. 11 (2018): 8754-8766.
11. Dittmer, Jürgen, and Benjamin Leyh. “Paracrine effects of stem cells in wound healing and cancer progression.” International journal of oncology44, no. 6 (2014): 1789-1798.
12. Walter, Merlin NM, Karina Therese Wright, Heidi R. Fuller, Sheila MacNeil, and William Eustace B. Johnson. “Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays.” Experimental cell research316, no. 7 (2010): 1271-1281.
13. Su, Vincent Yi-Fong, Chi-Shiuan Lin, Shih-Chieh Hung, and Kuang-Yao Yang. “Mesenchymal stem cell-conditioned medium induces neutrophil apoptosis associated with inhibition of the NF-κB pathway in endotoxin-induced acute lung injury.” International Journal of Molecular Sciences20, no. 9 (2019): 2208.
14. Mita, Tsuneyuki, Yoko Furukawa-Hibi, Hideyuki Takeuchi, Hisashi Hattori, Kiyofumi Yamada, Hideharu Hibi, Minoru Ueda, and Akihito Yamamoto. “Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer’s disease.” Behavioural Brain Research 293 (201