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      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

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          Abstract

          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.

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          Most cited references37

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          Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy.

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            Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use.

            We report a phase I trial to determine the feasibility of collection, ex vivo culture-expansion and intravneous infusion of human bone marrow-derived progenitor stromal cells (mesenchymal progenitor cells (MPCs)). Ten milliliter bone marrow samples were obtained from 23 patients with hematologic malignancies in complete remission. Bone marrow mononuclear cells were separated and adherent cells were culture-expanded in vitro for 4-7 weeks. Autologous MPCs were reinfused intravenously and a bone marrow examination repeated 2 weeks later for histologic assessment and in vitro hematopoietic cultures. Patient age ranged from 18 to 68 years and 12 subjects previously had undergone an autologous or syngeneic bone marrow transplant 4-52 months prior to collection of MPCs. A median of 364 x 10(6) nucleated bone marrow cells (range: 103 to 1004 x 10(6)) were used for ex vivo expansion. Median number of MPCs which were obtained after ex vivo culture expansion was 59.0 (range: 1.1 to 347 x 10(6)) representing a median cell doubling of 16,000-fold (13 doublings). Fifteen of 23 patients completed the ex vivo expansion and underwent MPC infusion. Time to infusion of MPCs after collection ranged from 28 to 49 days. Five patients in each of three groups were given 1, 10 and 50 x 10(6) MPCs. No adverse reactions were observed with the infusion of the MPCs. MPCs obtained from cancer patients can be collected, expanded in vitro and infused intravenously without toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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              Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta.

              In principle, transplantation of mesenchymal progenitor cells would attenuate or possibly correct genetic disorders of bone, cartilage and muscle, but clinical support for this concept is lacking. Here we describe the initial results of allogeneic bone marrow transplantation in three children with osteogenesis imperfecta, a genetic disorder in which osteoblasts produce defective type I collagen, leading to osteopenia, multiple fractures, severe bony deformities and considerably shortened stature. Three months after osteoblast engraftment (1.5-2.0% donor cells), representative specimens of trabecular bone showed histologic changes indicative of new dense bone formation. All patients had increases in total body bone mineral content ranging from 21 to 29 grams (median, 28), compared with predicted values of 0 to 4 grams (median, 0) for healthy children with similar changes in weight. These improvements were associated with increases in growth velocity and reduced frequencies of bone fracture. Thus, allogeneic bone marrow transplantation can lead to engraftment of functional mesenchymal progenitor cells, indicating the feasibility of this strategy in the treatment of osteogenesis imperfecta and perhaps other mesenchymal stem cell disorders as well.
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                Author and article information

                Contributors
                philippe.hernigou@wanadoo.fr
                Journal
                Int Orthop
                Int Orthop
                International Orthopaedics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0341-2695
                1432-5195
                9 October 2020
                : 1-19
                Affiliations
                GRID grid.412116.1, ISNI 0000 0001 2292 1474, Orthopedic Department Henri Mondor Hospital, , University Paris East, ; Paris, France
                Author information
                http://orcid.org/0000-0002-8475-279X
                Article
                4843
                10.1007/s00264-020-04843-z
                7546933
                33037446
                907b18ea-1d97-4e87-9bfb-a60363fd82ff
                © SICOT aisbl 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 26 September 2020
                : 29 September 2020
                Categories
                Orthopaedic Heritage

                Orthopedics
                bone marrow history,stem cells,osteonecrosis,marrow transplantation,tissue engineering
                Orthopedics
                bone marrow history, stem cells, osteonecrosis, marrow transplantation, tissue engineering

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