Regenerative Medicine & Therapeutics

Dr. Sharun Khan, BVSc. & AH, MVSc., Ph.D. (pursuing), CSIR-UGC NET, ICAR-NET

“We’re not made of drugs, we’re made of cells”  - Cade Hildreth

Stem cell therapy has already established a higher position in modern medicine thanks to its broad therapeutic applications. Among the different stem cell types, mesenchymal stem cells (MSCs) are being widely evaluated as therapeutic agents in veterinary and human medicine and constitute a significant part of regenerative medicine. It was initially hypothesized that MSCs affect the injured tissue by differentiating into specialized cells. However, later studies confirmed that only a small proportion of the transplanted cells survive and differentiate in host tissues. The majority of the therapeutic potential exhibited by MSCs is due to the paracrine effect on host cells mediated using cytokines, exosomes, growth factors, and extracellular matrix molecules

Adipose tissue-derived stromal vascular fraction (AdSVF) comprises a heterogeneous cell population, including the multipotent mesenchymal stem cells, hematopoietic stem cells, immune cells, endothelial cells, fibroblasts, and pericytes. As such, multipotent adipose tissue-derived mesenchymal stem cells (AdMSCs) are one of the important components of AdSVF. AdMSCs are multipotent adult mesenchymal cells isolated and cultured from the stromal vascular fraction derived from adipose tissue. There is a progressive increase in interest among the research community towards AdMSC, suggesting promising prospects in the coming years.

Sharun K, Jambagi K, Kumar R, Gugjoo MB, Pawde AM, Tuli HS, Dhama K, Amarpal. Clinical applications of adipose-derived stromal vascular fraction in veterinary practice. Vet Q. 2022 Dec;42(1):151-166. doi: 10.1080/01652176.2022.2102688. PMID: 35841195; PMCID: PMC9364732. https://doi.org/10.1080/01652176.2022.2102688

Freshly isolated AdSVF has exhibited promising osteogenic and vasculogenic capacities. AdSVF has already been proven to possess therapeutic potential for osteoarthritis management. It is also an attractive therapeutic option for enhancing wound healing. In addition, the combined use of AdSVF and platelet-rich plasma has an additive stimulatory effect in accelerating wound healing and can be considered an alternative to AdMSC treatment. It is also widely used for managing various orthopaedic conditions in clinical settings and has the potential for regenerating bone, cartilage, and tendons. Autologous AdSVF cells are used along with bone substitutes and other biological factors as an alternative to conventional bone grafting techniques owing to their promising osteogenic and vasculogenic capacity. It can also be used for treating osteonecrosis, meniscus tear, chondromalacia, and tendon injuries in veterinary practice. It has several advantages over in vitro expanded AdMSC, including precluding the need for culturing, reduced risk of cell contamination, and cost-effectiveness, making it ideal for clinical use. I am currently investigating the therapeutic potential of Pluronic F-127 composite hydrogel-loaded adipose-derived stromal vascular fraction (AdSVF), AdMSC, and conditioned medium (AdMSC-CM) for accelerating wound healing in full-thickness skin wounds using a rabbit model.

Cell-free therapy is the future of MSCs-based therapeutics as it overcomes the major limitations of cell-based therapy, including tumor differentiation and embolization. The future of MSC-based therapeutics is expected to be dominated by extracellular vesicles (EV). They are the key messenger between MSCs and damaged tissues and operate similarly to MSCs but lack the disadvantages of cell-based therapies. MSC-EVs have broad therapeutic applications in managing inflammatory diseases due to their potential for modulating the immune system and suppressing inflammatory responses. However, several challenges must be addressed concerning the standardization and characterization of different MSC-EV products. This will ensure the successful translation of MSC-EV-based cell-free therapy in clinical practice.

Sharun K, Dhama K, Jambagi K, Pawde AM, Amarpal. Cell-free Therapy for Inflammatory Diseases: Opportunities and Challenges. Recent Adv Inflamm Allergy Drug Discov. 2022;15(1):5-8. doi: 10.2174/2772270816666211220152218. PMID: 34931977. https://doi.org/10.2174/2772270816666211220152218

Platelets are the reservoir of growth factors and play a major role in several physiological processes, such as coagulation, angiogenesis, immune response, and tissue repair. Platelet concentrates are broadly classified into two groups depending on their fibrin content, namely platelet-rich plasma (PRP) and platelet-rich fibrin (PRF). PRP is plasma containing supra-physiological concentrations of the platelets. The growth factors present in the PRP play a crucial role in promoting local angiogenesis, regulation of cellular activity, stem cell homing, proliferation and differentiation of different stem cells, and deposition of matrix proteins contributing to tissue regeneration. PRP is used for managing corneal ulcers, corneal erosion, alkali burn, keratoconjunctivitis sicca, burn wounds, chronic wounds, cutaneous ulcers, acute traumatic bone fractures, tendinopathies, cartilage pathologies, osteoarthritis, and abdominal wall defects either as monotherapy or as an adjunctive therapeutic agent. In addition, PRP is widely used as a carrier of mesenchymal stem cells for transplanting into bone defects. Therefore, PRP therapy can be considered a simple, safe, and cost-effective method for treating various diseases and disorders in veterinary and human medicine.