The chapter "Mesenchymal Stem Cells: The Past, the Present, the Future" by Arnold I. Caplan provides a comprehensive overview of the development and applications of mesenchymal stem cells (MSCs). In the 1960s, Caplan's interest in MSCs was sparked by a lecture on collagen and its role in tadpole tail resorption, which influenced his research on the differentiation of embryonic chick limb mesodermal cells. This early work laid the foundation for understanding the molecular control of cell differentiation. In the late 1960s and early 1980s, Caplan and colleagues used chick limb bud cell culture systems to purify molecules that stimulate chondrogenesis, leading to the discovery of bone morphogenetic proteins (BMPs). This discovery challenged the prevailing belief that adult stem cells were limited to hematopoietic stem cells (HSCs) and germ cells. Caplan proposed the concept of adult MSCs, which could be used for tissue engineering and regenerative medicine. The present section highlights the clinical applications of MSCs, such as their use in bone marrow transplantation to enhance engraftment and hematopoietic recovery. MSCs have also shown promise in treating autoimmune diseases like graft-versus-host disease and inflammatory bowel disease due to their immunomodulatory properties. Additionally, MSCs have been explored for treating chronic conditions like asthma and multiple sclerosis by modulating inflammation and promoting tissue regeneration. The future section discusses the potential of MSCs in addressing a wide range of diseases, including diabetes, skin regeneration after burns, stroke, spinal cord injuries, and acute organ failure. The chapter also explores the emerging idea that all MSCs may be pericytes, cells that reside on blood vessels and play a crucial role in maintaining vascular health and tissue regeneration. Overall, the chapter underscores the evolving role of MSCs in both basic research and clinical applications, highlighting their potential to revolutionize regenerative medicine.The chapter "Mesenchymal Stem Cells: The Past, the Present, the Future" by Arnold I. Caplan provides a comprehensive overview of the development and applications of mesenchymal stem cells (MSCs). In the 1960s, Caplan's interest in MSCs was sparked by a lecture on collagen and its role in tadpole tail resorption, which influenced his research on the differentiation of embryonic chick limb mesodermal cells. This early work laid the foundation for understanding the molecular control of cell differentiation. In the late 1960s and early 1980s, Caplan and colleagues used chick limb bud cell culture systems to purify molecules that stimulate chondrogenesis, leading to the discovery of bone morphogenetic proteins (BMPs). This discovery challenged the prevailing belief that adult stem cells were limited to hematopoietic stem cells (HSCs) and germ cells. Caplan proposed the concept of adult MSCs, which could be used for tissue engineering and regenerative medicine. The present section highlights the clinical applications of MSCs, such as their use in bone marrow transplantation to enhance engraftment and hematopoietic recovery. MSCs have also shown promise in treating autoimmune diseases like graft-versus-host disease and inflammatory bowel disease due to their immunomodulatory properties. Additionally, MSCs have been explored for treating chronic conditions like asthma and multiple sclerosis by modulating inflammation and promoting tissue regeneration. The future section discusses the potential of MSCs in addressing a wide range of diseases, including diabetes, skin regeneration after burns, stroke, spinal cord injuries, and acute organ failure. The chapter also explores the emerging idea that all MSCs may be pericytes, cells that reside on blood vessels and play a crucial role in maintaining vascular health and tissue regeneration. Overall, the chapter underscores the evolving role of MSCs in both basic research and clinical applications, highlighting their potential to revolutionize regenerative medicine.