Bone marrow in orthopaedics (part II): a three hundred and seventy million-year saga from the Devonian to the coronavirus disease 2019 pandemic—osteonecrosis; transplantation; “human chimera”; stem cells, bioreactors, and coronavirus disease

PURPOSE: Three hundred seventy million years ago, bone marrow appeared in skeleton of a fish. More than one hundred years ago, the concept of bone marrow transplantation was proposed to treat human diseases. During the last five decades, this concept became a reality first in hematology and later for orthopaedic diseases. MATERIAL AND METHODS: These advances were possible due to the comprehension of the three major components of bone marrow: the fat part, the haematologic part, and the stroma part. Each part has a different history, but the three parts are linked in physiology as in history. RESULTS: During many centuries, bone marrow was considered just as food; however, one hundred years ago, the concept of bone marrow transplantation to treat humans was proposed by the French physician Brown-Séquard. During the last five decades, this concept became a reality first in haematology and later for orthopaedic diseases. Transferring what was known from experimental animal models to humans was met with many challenges, the atomic bomb research, and many deaths. Yet through the recognition and subsequent understanding of fundamental processes, medical resiliency, and the determination of a few pioneers, local bone marrow transplantation in orthopaedic surgery became a therapeutic option first for a limited number of diseases and patients. Over the last two decades, mesenchymal stromal cells (MSCs) have been the focus of intense research by acadaemia and industry due to their unique features. MSCs can be easily isolated and expanded through in vitro culture by taking full advantage of their self-renewing capacity. In addition, MSCs exert immunomodulatory effects and can be differentiated into various lineages, which makes them highly attractive for clinical applications in cell-based therapies. CONCLUSION: In this review, we attempted to provide a historical overview of bone marrow history, MSC discovery, characterization, and the first clinical studies conducted.