Mesenchymal stem cells (MSCs) have evolved from their initial discovery in the 1960s to become a significant area of research and clinical application. In 1964, Arnold I. Caplan was inspired by a lecture on collagen and its role in development, which led him to study embryonic chick limb mesodermal cells. These cells, later identified as MSCs, could differentiate into various mesodermal phenotypes based on culture conditions. In the late 1960s, Caplan demonstrated that the initial plating density of these cells controlled cartilage formation, and in the 1970s and 1980s, he and colleagues used chick limb bud cell cultures to purify molecules that stimulated chondrogenesis, later identified as BMPs. In the 1980s, Caplan proposed the existence of adult MSCs, challenging the prevailing belief that only hematopoietic stem cells existed in adults. This led to the development of tissue engineering approaches using MSCs with scaffolds to regenerate tissues like cartilage and tendon. MSCs have been used in animal models and some human trials to repair cartilage defects. In the present, MSCs are recognized for their immunomodulatory properties, which have led to their use in clinical trials for graft-versus-host disease and inflammatory bowel disease. Although their ability to differentiate into bone and cartilage remains important for tissue engineering, their immunomodulatory effects are more impactful in treating chronic inflammation in conditions like osteoarthritis and rheumatoid arthritis. Looking to the future, MSCs are being explored for their potential in treating autoimmune diseases, promoting scarless skin regeneration, and repairing injuries to the nervous system, heart, and kidneys. Recent research suggests that MSCs may be pericytes, which play a role in regulating the immune system and promoting tissue regeneration. The future of MSC therapy holds promise for revolutionizing medicine through their ability to modulate immune responses and promote tissue repair.Mesenchymal stem cells (MSCs) have evolved from their initial discovery in the 1960s to become a significant area of research and clinical application. In 1964, Arnold I. Caplan was inspired by a lecture on collagen and its role in development, which led him to study embryonic chick limb mesodermal cells. These cells, later identified as MSCs, could differentiate into various mesodermal phenotypes based on culture conditions. In the late 1960s, Caplan demonstrated that the initial plating density of these cells controlled cartilage formation, and in the 1970s and 1980s, he and colleagues used chick limb bud cell cultures to purify molecules that stimulated chondrogenesis, later identified as BMPs. In the 1980s, Caplan proposed the existence of adult MSCs, challenging the prevailing belief that only hematopoietic stem cells existed in adults. This led to the development of tissue engineering approaches using MSCs with scaffolds to regenerate tissues like cartilage and tendon. MSCs have been used in animal models and some human trials to repair cartilage defects. In the present, MSCs are recognized for their immunomodulatory properties, which have led to their use in clinical trials for graft-versus-host disease and inflammatory bowel disease. Although their ability to differentiate into bone and cartilage remains important for tissue engineering, their immunomodulatory effects are more impactful in treating chronic inflammation in conditions like osteoarthritis and rheumatoid arthritis. Looking to the future, MSCs are being explored for their potential in treating autoimmune diseases, promoting scarless skin regeneration, and repairing injuries to the nervous system, heart, and kidneys. Recent research suggests that MSCs may be pericytes, which play a role in regulating the immune system and promoting tissue regeneration. The future of MSC therapy holds promise for revolutionizing medicine through their ability to modulate immune responses and promote tissue repair.