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Bone Marrow as a Source of Cells for Musculoskeletal Cellular Therapies

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Orthobiologics

Abstract

Bone marrow provides an invaluable source of cells for cell-based therapies in the orthopedic setting. Bone marrow aspirates (BMAs) contain a diversity of stem and progenitor cell systems, including connective tissue progenitors (CTPs), hematopoietic stem and progenitor cells (HSCs), and progenitors of vascular endothelium (EPCs). Bone marrow can be harvested by percutaneous minimally invasive aspiration or excavation with minimal morbidity. With appropriate anticoagulation, this provides a cell suspension that can be readily processed through a variety of methods.

BMA has a long clinical history as a means of supplementing areas of bone healing as a form of autologous bone grafts, with or without processing, presumably repeating deficient populations of osteoblastic connective tissue progenitors. Processed marrow can be provided as a point of care product. However, the specific indications and optimal processing methods and composition for bone marrow-derived cells for specific indications have yet to be determined. Processed marrow can also provide the starting materials needed for in vitro culture expansion and fabrication of a diversity of cellular and cell-derived products.

BMA is most frequently performed from the iliac crest. Yield of CTPs and other marrow-derived cells can be strongly influenced by patient selection, aspiration site, aspiration technique, and subsequent processing. Various processing methods have been developed for the concentration of BMA including density separation, selective retention, magnetic separation, and fluorescence-activated cell sorting (FACS).

Consensus standards are needed for analysis and reporting on BMA and BMA-derived product composition and the efficacy of processing methods (yield, concentration, prevalence, etc.) and will accelerate the development and comparison of novel treatments. Linking clinical data (demographics, diagnosis, disease stage, comorbidities, and functional status) and BMA harvest and composition data, together with rigorously documented clinical outcomes, is a key step in this process.

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References

  1. Piuzzi NS, Hussain ZB, Chahla J, et al. Variability in the preparation, reporting, and use of bone marrow aspirate concentrate in musculoskeletal disorders: a systematic review of the clinical orthopaedic literature. J Bone Joint Surg Am Vol. 2018;100(6):517–25.

    Google Scholar 

  2. Piuzzi NS, Khlopas A, Newman JM, et al. Bone marrow cellular therapies: novel therapy for knee osteoarthritis. J Knee Surg. 2018;31(1):22–6.

    Google Scholar 

  3. Piuzzi NS, Chahla J, Jiandong H, et al. Analysis of cell therapies used in clinical trials for the treatment of osteonecrosis of the femoral head: a systematic review of the literature. J Arthroplast. 2017;32(8):2612–8.

    Google Scholar 

  4. Marcucio RS, Nauth A, Giannoudis PV, et al. Stem cell therapies in orthopaedic trauma. J Orthop Trauma. 2015;29:S24–7.

    Google Scholar 

  5. Lindholm TS, Urist MR. A quantitative analysis of new bone formation by induction in compositive grafts of bone marrow and bone matrix. Clin Orthop Relat Res. 1980;150:288–300.

    Article  Google Scholar 

  6. Connolly JF, Shindell R. Percutaneous marrow injection for an ununited tibia. Nebr Med J. 1986;71(4):105–7.

    CAS  PubMed  Google Scholar 

  7. Connolly JF, Guse R, Tiedeman J, Dehne R. Autologous marrow injection as a substitute for operative grafting of tibial nonunions. Clin Orthop Relat Res. 1991;266:259–70.

    Google Scholar 

  8. Gangji V, De Maertelaer V, Hauzeur J-P. Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: five year follow-up of a prospective controlled study. Bone. 2011;49(5):1005–9.

    Google Scholar 

  9. Hernigou P, Flouzat-Lachaniette CH, Delambre J, et al. Osteonecrosis repair with bone marrow cell therapies: state of the clinical art. Bone. 2014;70:102–9.

    Google Scholar 

  10. Yoshioka T, Mishima H, Akaogi H, Sakai S, Li M, Ochiai N. Concentrated autologous bone marrow aspirate transplantation treatment for corticosteroid-induced osteonecrosis of the femoral head in systemic lupus erythematosus. Int Orthop. 2011;35(6):823–9.

    Google Scholar 

  11. Piuzzi NS, Chahla J, Schrock JB, et al. Evidence for the use of cell-based therapy for the treatment of osteonecrosis of the femoral head: a systematic review of the literature. J Arthroplast. 2017;32(5):1698–708.

    Google Scholar 

  12. Piuzzi NS, Chahla J, Jiandong H, et al. Analysis of cell therapies used in clinical trials for the treatment of osteonecrosis of the femoral head: a systematic review of the literature. J Arthroplast. 2017;32(8):2612–8.

    Google Scholar 

  13. Hernigou P, Mathieu G, Poignard A, Manicom O, Beaujean F, Rouard H. Percutaneous autologous bone-marrow grafting for nonunions. Surgical technique. J Bone Joint Surg. 2006;88-A(Supplement 1, Part 2):322–7.

    Article  Google Scholar 

  14. Sugaya H, Mishima H, Aoto K, et al. Percutaneous autologous concentrated bone marrow grafting in the treatment for nonunion. Eur J Orthop Surg Traumatol. 2013;24(5):671–8.

    Google Scholar 

  15. Fernandez-Bances I, Perez-Basterrechea M, Perez-Lopez S, et al. Repair of long-bone pseudoarthrosis with autologous bone marrow mononuclear cells combined with allogenic bone graft. Cytotherapy. 2013;15(5):571–7.

    Google Scholar 

  16. Garg NK, Gaur S. Percutaneous autogenous bone-marrow grafting in congenital tibial pseudarthrosis. J Bone Joint Surg Br. 1995;77(5):830–1.

    Article  CAS  Google Scholar 

  17. Goel A, Sangwan SS, Siwach RC, Ali AM. Percutaneous bone marrow grafting for the treatment of tibial non-union. Injury. 2005;36(1):203–6.

    Google Scholar 

  18. Jäger M, Herten M, Fochtmann U, et al. Bridging the gap: bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects. J Orthop Res. 2011;29(2):173–80.

    Google Scholar 

  19. Petri M, Namazian A, Wilke F, et al. Repair of segmental long-bone defects by stem cell concentrate augmented scaffolds: a clinical and positron emission tomography—computed tomography analysis. Int Orthop. 2013;37(11):2231–7.

    Google Scholar 

  20. Gessmann J, Köller M, Godry H, Schildhauer TA, Seybold D. Regenerate augmentation with bone marrow concentrate after traumatic bone loss. Orthop Rev (Pavia). 2012;4:1.

    Google Scholar 

  21. Khashan M, Inoue S, Berven SH. Cell based therapies as compared to autologous bone grafts for spinal arthrodesis. Spine (Phila Pa 1976). 2013;38(21):1885–91.

    Google Scholar 

  22. Lee DH, Ryu KJ, Kim JW, Kang KC, Choi YR. Bone marrow aspirate concentrate and platelet-rich plasma enhanced bone healing in distraction osteogenesis of the tibia. Clin Orthop Relat Res. Published online. 2014:1–9.

    Google Scholar 

  23. Gobbi A, Karnatzikos G, Sankineani SR. One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med. 2014;42(3):648–57.

    Google Scholar 

  24. Buda R, Vannini F, Castagnini F, et al. Regenerative treatment in osteochondral lesions of the talus: autologous chondrocyte implantation versus one-step bone marrow derived cells transplantation. Int Orthop. Published online. 2015:893–900.

    Google Scholar 

  25. Giannini S, Buda R, Battaglia M, et al. One-step repair in talar osteochondral lesions: 4-year clinical results and T2-mapping capability in outcome prediction. Am J Sports Med. 2012;41(3):511–8.

    Google Scholar 

  26. Do KJ, Lee GW, Jung GH, et al. Clinical outcome of autologous bone marrow aspirates concentrate (BMAC) injection in degenerative arthritis of the knee. Eur J Orthop Surg Traumatol. Published online. 2014:1–7.

    Google Scholar 

  27. Wong KL, Lee KBL, Tai BC, Law P, Lee EH, Hui JHP. Injectable cultured bone marrow–derived mesenchymal stem cells in Varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up. Arthrosc J Arthrosc Relat Surg. 2013;29(12):2020–8.

    Google Scholar 

  28. Chahla J, Piuzzi NS, Mitchell JJ, et al. Intra-articular cellular therapy for osteoarthritis and focal cartilage defect of the knee. J Bone Joint Surg. 2016;98:1511–21.

    Article  Google Scholar 

  29. Piuzzi NS, Khlopas A, Newman JM, et al. Bone marrow cellular therapies: novel therapy for knee osteoarthritis. J Knee Surg. 2018;31(1):22–6.

    Google Scholar 

  30. Pascual-Garrido C, Rolón A, Makino A. Treatment of chronic patellar tendinopathy with autologous bone marrow stem cells: a 5-year-followup. Stem Cells Int. 2012:953510.

    Google Scholar 

  31. Stein BE, Stroh DA, Schon LC. Outcomes of acute Achilles tendon rupture repair with bone marrow aspirate concentrate augmentation. Int Orthop. 2015;39:901–5.

    Google Scholar 

  32. Muschler GF, Midura RJ. Connective tissue progenitors: practical concepts for clinical applications. Clin Orthop Relat Res. 2002;1(395):66–80.

    Google Scholar 

  33. Mantripragada VP, Bova WA, Piuzzi NS, et al. Native-osteoarthritic joint resident stem and progenitor cells for cartilage cell-based therapies: a quantitative comparison with respect to concentration and biological performance. Am J Sports Med. Published online. 2019:1–10.

    Google Scholar 

  34. Brighton CT, Lorich DG, Kupcha R, Reilly TM, Jones AR, Woodbury RA. The pericyte as a possible osteoblast progenitor cell. Clin Orthop Relat Res. 1992;275:287–99.

    Google Scholar 

  35. Connolly J, Guse R, Lippiello L, Dehne R. Development of an osteogenic bone-marrow preparation. J Bone Joint Surg Am. 1989;71(5):684–91.

    Article  CAS  Google Scholar 

  36. Gimble JM, Robinson CE, Wu X, Kelly KA. The function of adipocytes in the bone marrow stroma: an update. Bone. 1996;19(5):421–8.

    Article  CAS  Google Scholar 

  37. Huard C, Moisset PA, Dicaire A, et al. Transplantation of dermal fibroblasts expressing MyoD1 in mouse muscles. Biochem Biophys Res Commun. 1998;248(3):648–54.

    Google Scholar 

  38. O’Driscoll SW. Articular cartilage regeneration using periosteum. Clin Orthop Relat Res. 1999;367(Suppl):S186–203.

    Article  Google Scholar 

  39. Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg. 1997;79-A:1699–709.

    Google Scholar 

  40. Mantripragada VP, Bova WA, Boehm C, et al. Primary cells isolated from human knee cartilage reveal decreased prevalence of progenitor cells but comparable biological potential during osteoarthritic disease progression. J Bone Joint Surg. 2018;100:1771–80.

    Article  CAS  Google Scholar 

  41. Mantripragada VP, Bova WA, Boehm C, et al. Progenitor cells from different zones of human cartilage and their correlation with histopathological osteoarthritis progression. J Orthop Res. 2018;36(6):1728–38.

    Google Scholar 

  42. Mantripragada VP, Boehm C, Bova W, Briskin I, Piuzzi NS, Muschler GF. Patient age and cell concentration influence prevalence and concentration of progenitors in bone marrow aspirates: an analysis of 436 patients. J Bone Joint Surg. Published online. 2021:1–9.

    Google Scholar 

  43. Qadan MA, Piuzzi NS, Boehm C, et al. Variation in primary and culture-expanded cells derived from connective tissue progenitors in human bone marrow space, bone trabecular surface and adipose tissue. Cytotherapy. 2018;20(3):343–60.

    Google Scholar 

  44. Mantripragada VP, Bova W, Boehm C, et al. Primary cells isolated from human knee cartilage reveal decreased prevalence of progenitors cells but comparable biological potential during osteoarthritic disease progression. J Bone Joint Surg Am Vol. Published online Accepted. 2018;100(20):1771–80.

    Google Scholar 

  45. Mantripragada VP, Piuzzi NS, Bova WA, et al. Donor-matched comparison of chondrogenic progenitors resident in human infrapatellar fat pad, synovium, and periosteum - implications for cartilage repair. Connect Tissue Res. 2019;60(6):597–610.

    Google Scholar 

  46. Mantripragada VP, Boehm C, Bova W, Briskin I, Piuzzi NS, Muschler GF. Patient age and cell concentration influence prevalence and concentration of progenitors in bone marrow aspirates: an analysis of 436 patients. J Bone Joint Surg. Published online. 2021:1–9.

    Google Scholar 

  47. Mantripragada VP, Tan K-L, Vasavada S, Bova W, Barnard J, Muschler GF. Characterization of heterogeneous primary human cartilage-derived cell population using non-invasive live-cell phase-contrast time-lapse imaging. Cytotherapy. 2020:1–12.

    Google Scholar 

  48. Caralla T, Boehm C, Hascall V, Muschler G. Hyaluronan as a novel marker for rapid selection of connective tissue progenitors. Ann Biomed Eng. 2012;40(12):2559–67.

    Google Scholar 

  49. Chan CKF, Gulati GS, Sinha R, et al. Identification of the human skeletal stem cell. Cell. 2018;175(1):43–56.e21.

    Google Scholar 

  50. Kim EJ, Fleischman AJ, Muschler GF, Roy S. Response of bone marrow derived connective tissue progenitor cell morphology and proliferation on geometrically modulated microtextured substrates. Biomed Microdevices. 2013;15(3):385–96.

    Google Scholar 

  51. Muschler GF, Matsukura Y, Nitto H, et al. Selective retention of bone marrow-derived cells to enhance spinal fusion. Clin Orthop Relat Res. 2005;432:242–51.

    Google Scholar 

  52. McLain RF, Fleming JE, Boehm CA, Muschler GF. Aspiration of osteoprogenitor cells for augmenting spinal fusion: comparison of progenitor cell concentrations from the vertebral body and iliac crest. J Bone Joint Surg Am. 2005;87(12):2655–61.

    Google Scholar 

  53. Muschler GF, Nakamoto C, Griffith LG. Engineering principles of clinical cell-based tissue engineering. J Bone Joint Surg Ser A. 2004;86(7):1541–58.

    Google Scholar 

  54. Muschler GF, Midura RJ, Nakamoto C. Practical modeling concepts for connective tissue stem cell and progenitor compartment kinetics. J Biomed Biotechnol. 2003;2003(3):170–93.

    Google Scholar 

  55. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7.

    Google Scholar 

  56. Krampera M, Galipeau J, Shi Y, Tarte K, Sensebe L. Immunological characterization of multipotent mesenchymal stromal cells-the international society for cellular therapy (ISCT) working proposal. Cytotherapy. 2013;15(9):1054–61.

    Google Scholar 

  57. Hernigou P, Poignard A, Rouard H. Percutaneous autologous bone-marrow grafting for nonunions: influence of the number and concentration of progenitor cells. J Bone Joint Surg. 2005;87-A(7):1430–7.

    Google Scholar 

  58. Piuzzi N, Ng M, Chughtai M, et al. The stem-cell market for the treatment of knee osteoarthritis: a patient perspective. J Knee Surg. 2018;31(6):551–6.

    Google Scholar 

  59. Phemister DB. The fate of transplanted bone and regenerative power of its various constituents. Surg Gynecol Obstetr. 1914;19:303–14.

    Google Scholar 

  60. Phemister DB. Treatment of the necrotic head of the femur in adults. J Bone Joint Surg. 1949;31(1):55–66.

    Google Scholar 

  61. BURWELL RG. Studies in the transplantation of bone. V. the capacity of fresh and treated homografts of bone to evoke transplantation immunity. J Bone Joint Surg Br. 1963;45 B:386–401.

    Google Scholar 

  62. Mauffrey C, Barlow BT, Smith W. Management of segmental bone defects. J Am Acad Orthop Surg. 2015;23(3):143–53.

    PubMed  Google Scholar 

  63. Pape HC, Evans A, Kobbe P. Autologous bone graft: properties and techniques. J Orthop Trauma. 2010;24(SUPPL. 1):36–40.

    Google Scholar 

  64. Younger EM, Chapman MW. Morbidity at bone graft donor sites. J Orthop Trauma. 1989;3(3):192–5.

    Google Scholar 

  65. Robertson PA, Wray AC. Natural history of posterior iliac crest bone graft donation for spinal surgery: a prospective analysis of morbidity. Spine (Phila Pa 1976). 2001;26(13):1473–6.

    Article  CAS  Google Scholar 

  66. Banwart JC, Asher MA, Hassanein RS. Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. Spine (Phila Pa 1976). 1995;20(9):1055–60.

    Article  CAS  Google Scholar 

  67. Urgery S, Ncorporated I. Prospective observational study of donor-site. J Bone Joint Surg. 2012;94(18):1649–54.

    Google Scholar 

  68. Piuzzi NS, Mantripragada VP, Kwee E, et al. Bone marrow-derived cellular therapies in orthopaedics part 1: recommendations for bone marrow aspiration technique and safety. JBJS Rev. 2018;6(11):e5.

    Google Scholar 

  69. Steadman RJ, Rodkey WG, Rodrigo JJ. Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop Relat Res. 2001;391S:S362–9.

    Article  Google Scholar 

  70. Cole BBJ, Pascual-garrido C, Grumet RC. Surgical Management of Articular Cartilage Defects in the knee. J Bone Joint Surg. 2009;91(7):1778–90.

    Google Scholar 

  71. Hoyt BW, Pavey GJ, Potter BK, Forsberg JA. Heterotopic ossification and lessons learned from fifteen years at war: a review of therapy, novel research, and future directions for military and civilian orthopaedic trauma. Bone. 2018;109:3–11.

    Google Scholar 

  72. Forsberg JA, Pepek JM, Wagner S, et al. Heterotopic ossification in high-energy wartime extremity injuries: prevalence and risk factors. J Bone Joint Surg Ser A. 2009;91(5):1084–91.

    Google Scholar 

  73. Shankar A, Daniel RT, Walter N, Chandy MJ. Heterotopic ossification in the orbit. Surg Neurol. 2002;58(6):421–3.

    Google Scholar 

  74. Jäger M, Hernigou P, Zilkens C, et al. Cell therapy in bone healing disorders. Orthop Rev (Pavia). 2010;2(2):e20.

    Google Scholar 

  75. Papathanasopoulos A, Kouroupis D, Henshaw K, McGonagle D, Jones EA, Giannoudis PV. Effects of antithrombotic drugs fondaparinux and tinzaparin on in vitro proliferation and osteogenic and chondrogenic differentiation of bone-derived mesenchymal stem cells. J Orthop Res. 2011;29(9):1327–35.

    Google Scholar 

  76. Do Amaral RJFC, Da Silva NP, Haddad NF, et al. Platelet-rich plasma obtained with different anticoagulants and their effect on platelet numbers and mesenchymal stromal cells behavior in vitro. Stem Cells Int. 2016:7414036.

    Google Scholar 

  77. Luangphakdy V, Boehm C, Pan H, Herrick J, Zaveri P, Muschler GF. Assessment of methods for rapid intraoperative concentration and selection of marrow-derived connective tissue progenitors for bone regeneration using the canine femoral multidefect model. Tissue Eng Part A. 2016;22(1–2):17–30.

    Google Scholar 

  78. Meppelink AM, Wang XH, Bradica G, et al. Rapid isolation of bone marrow mesenchymal stromal cells using integrated centrifuge-based technology. Cytotherapy. 2016;18(6):729–39.

    Google Scholar 

  79. Muschler GF, Matsukura Y, Nitto H, et al. Selective retention of bone marrow-derived cells to. Clin Orthop Relat Res. 2005;432:242–51.

    Google Scholar 

  80. Chu W, Zhuang Y, Gan Y, Wang X, Tang T, Dai K. Comparison and characterization of enriched mesenchymal stem cells obtained by the repeated filtration of autologous bone marrow through porous biomaterials. J Transl Med. 2019;17(1):1–16.

    Google Scholar 

  81. Luo K, Gao X, Gao Y, et al. Multiple integrin ligands provide a highly adhesive and osteoinductive surface that improves selective cell retention technology. Acta Biomater. 2019;85:106–16.

    Google Scholar 

  82. Luangphakdy V, Boehm C, Pan H, Herrick J, Zaveri P, Muschler GF. Assessment of methods for rapid intraoperative concentration and selection of marrow-derived connective tissue progenitors for bone regeneration using the canine femoral multidefect model. Tissue Eng Part A. 2016;22(1–2).

    Google Scholar 

  83. Yousef MAA, La Maida GA, Misaggi B. Long-term radiological and clinical outcomes after using bone marrow mesenchymal stem cells concentrate obtained with selective retention cell technology in posterolateral spinal fusion. Spine (Phila Pa 1976). 2017;42(24):1871–9.

    Google Scholar 

  84. Yang P, Xing J, Chen B, et al. The clinical use of the enriched bone marrow obtained by selective cell retention technology in treating adolescent idiopathic scoliosis. J Orthop Transl. 2021;27(September 2019):146–52.

    Google Scholar 

  85. Caralla T, Joshi P, Fleury S. et al, In vivo transplantation of autogenous marrow-derived cells following rapid intraoperative magnetic separation based on hyaluronan to augment bone regeneration.

    Google Scholar 

  86. Jia Z, Liang Y, Xu X, et al. Isolation and characterization of human mesenchymal stem cells derived from synovial fluid by magnetic-activated cell sorting (MACS). Cell Biol Int. 2018;42(3):262–71.

    Google Scholar 

  87. Petters O, Schmidt C, Thuemmler C, et al. Point-of-care treatment of focal cartilage defects with selected chondrogenic mesenchymal stromal cells—an in vitro proof-of-concept study. J Tissue Eng Regen Med. 2018;12(7):1717–27.

    Google Scholar 

  88. Piuzzi NS, Mantripragada VP, Kwee E, et al. Bone marrow-derived cellular therapies in orthopaedics part 2: recommendations for reporting the quality of bone marrow-derived cell populations. JBJS Rev. 2018;6(11):e5.

    Google Scholar 

  89. McLain RF, Fleming JE, Boehm CA, Muschler GF. Aspiration of osteoprogenitor cells for augmenting spinal fusion: comparison of progenitor cell concentrations from the vertebral body and iliac crest. J Bone Joint Surg Ser A. 2005;87(12 I):2655–61.

    Google Scholar 

  90. Hernigou J, Alves A, Homma Y, Guissou I, Hernigou P. Anatomy of the ilium for bone marrow aspiration: map of sectors and implication for safe trocar placement. Int Orthop. 2014;38(12):2585–90.

    Google Scholar 

  91. Hernigou J, Picard L, Alves A, Silvera J, Homma Y, Hernigou P. Understanding bone safety zones during bone marrow aspiration from the iliac crest: the sector rule. Int Orthop. 2014;38(11):2377–84.

    Google Scholar 

  92. Pierini M, Di Bella C, Dozza B, et al. The posterior iliac crest outperforms the anterior iliac crest when obtaining mesenchymal stem cells from bone marrow. J Bone Joint Surg Am. 2013;95(12):1101–7.

    Google Scholar 

  93. Patterson TE, Boehm C, Nakamoto C, et al. The efficiency of bone marrow aspiration for the harvest of connective tissue progenitors from the human iliac crest. J Bone Joint Surg Am. 2017;99:19.

    Google Scholar 

  94. Hernigou P, Homma Y, Flouzat Lachaniette CH, et al. Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop. 2013;37(11):2279–87.

    Google Scholar 

  95. Haseler LJ, Sibbitt RR, Sibbitt WL, et al. Syringe and needle size, syringe type, vacuum generation, and needle control in aspiration procedures. Cardiovasc Interv Radiol. 2011;34(3):590–600.

    Google Scholar 

  96. Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Ser A. 1997;79(11):1699–709.

    Google Scholar 

  97. Patterson TE, Boehm C, Nakamoto C, et al. The efficiency of bone marrow aspiration for the harvest of connective tissue progenitors from the human iliac crest. J Bone Joint Surg Am. 2017;99:1673–82.

    Google Scholar 

  98. Jillella AP, Ustun C. What is the optimum number of CD34+ peripheral blood stem cells for an autologous transplant? Stem Cells Dev. 2004;13(6):598–606.

    Google Scholar 

  99. Hernigou P, Desroches A, Queinnec S, et al. Morbidity of graft harvesting versus bone marrow aspiration in cell regenerative therapy. Int Orthop. 2014;38(9):1855–60.

    Google Scholar 

  100. Bain BJ. Bone marrow biopsy morbidity and mortality. Br J Haematol. 2003;121(6):949–51.

    Google Scholar 

  101. Bain BJ. Bone marrow biopsy morbidity and mortality: 2002 data. Clin Lab Haematol. 2004;26(5):315–8.

    Google Scholar 

  102. Bain BJ. Bone marrow biopsy morbidity: review of 2003. J Clin Pathol. 2005;58(4):406–8.

    Google Scholar 

  103. Majors AK, Boehm CA, Nitto H, Midura RJ, Muschler GF. Characterization of human bone marrow stromal cells with respect to osteoblastic differentiation. J Orthop Res. 1997;15(4):546–57.

    Google Scholar 

  104. Gaul F, Bugbee WD, Hoenecke HR, D’Lima DD. A review of commercially available point-of-care devices to concentrate bone marrow for the treatment of osteoarthritis and focal cartilage lesions. Cartilage. 2019;10(4):387–94.

    Google Scholar 

  105. Dragoo JL, Guzman RA. Evaluation of the consistency and composition of commercially available bone marrow aspirate concentrate systems. Orthop J Sport Med. 2020;8(1):1–8.

    Google Scholar 

  106. Muschler GF. Methods of preparing a composite bone graft. Published online 1998.

    Google Scholar 

  107. Muschler GF. Apparatus and methods for preparing an implantable graft. Published online 2000.

    Google Scholar 

  108. Caralla T, Joshi P, Fleury S, et al. In vivo transplantation of autogenous marrow-derived cells following rapid intraoperative magnetic separation based on hyaluronan to augment bone regeneration. Tissue Eng Part A. 2013;19(1–2):125–34.

    Google Scholar 

  109. Murray I, Chahla J, Safran M, et al. International expert consensus on a cell therapy communication tool: DOSES. J Bone Joint Surg. 2019;101:904–11.

    Google Scholar 

  110. Mantripragada VP, Piuzzi NS, George J, et al. Reliable assessment of bone marrow and bone marrow concentrates using automated hematology analyzer. Regen Med. 2021;14(7):639–46.

    Google Scholar 

  111. Bidula J, Boehm C, Powell K, et al. Osteogenic progenitors in bone marrow aspirates from smokers and nonsmokers. Clin Orthop Relat Res. 2006;442:252–9.

    Google Scholar 

  112. Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am. 1997;79(11):1699–709.

    Google Scholar 

  113. McLain RF, Boehm CA, Rufo-Smith C, Muschler GF. Transpedicular aspiration of osteoprogenitor cells from the vertebral body: progenitor cell concentrations affected by serial aspiration. Spine J. 2009;9(12):995–1002.

    Google Scholar 

  114. ASTM F2944 - 20. Standard practice for automated colony forming unit (CFU) assays—image acquisition and analysis method for enumerating and characterizing cells and colonies in culture. ASTM Int. Published online. 2020.

    Google Scholar 

  115. Mantripragada VR, Luagphakdy V, Kwee E, Piuzzi N, Powell K, Muschler G. Automated imaging and analysis of colony founding stem and progenitor cells—correlation of early quality attributes with future biological performance. Cytotherapy. 2017;19(5):S119.

    Google Scholar 

  116. Powell K, Nakamoto C, Villarruel S, Boahm C, Muschler G. Quantitative image analysis of connective tissue progenitors. Anal Quant Cytol Histol. Published online. 2007:112–21.

    Google Scholar 

  117. Kwee E, Saidel G, Powell K, Heylman C, Boehm C, Muschler G. Quantifying proliferative and surface marker heterogeneity in colony-founding connective tissue progenitors and their progeny using time-lapse microscopy. J Tissue Eng Regen Med. 2019;13(2):203–16.

    Google Scholar 

  118. Piuzzi NS, Dominici M, Long M, et al. Proceedings of the signature series symposium “cellular therapies for orthopaedics and musculoskeletal disease proven and unproven therapies—promise, facts and fantasy,” international society for cellular therapies, Montreal, Canada, may 2, 2018. Cytotherapy. 2018;20(11):1381–400.

    Google Scholar 

  119. Chu CR, Rodeo S, Bhutani N, et al. Optimizing clinical use of biologics in orthopaedic surgery: consensus recommendations from the 2018 AAOS/NIH U-13 conference. J Am Acad Orthop Surg. 2019;27(2):E50–63.

    Google Scholar 

  120. Freeman BT, Jung JP, Ogle BM. Single-cell RNA-Seq of bone marrow-derived mesenchymal stem cells reveals unique profiles of lineage priming. PLoS One. 2015;10:9.

    Google Scholar 

  121. Wolock SL, Krishnan I, Tenen DE, et al. Mapping distinct bone marrow niche populations and their differentiation paths. Cell Rep. 2019;28(2):302–11.e5.

    Google Scholar 

  122. Tikhonova AN, Dolgalev I, Hu H, et al. The bone marrow microenvironment at single-cell resolution. Nature. 2019;569(7755):222–8.

    Google Scholar 

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Correspondence to George F. Muschler .

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Muschler, G.F., Simmons, H., Mantripragada, V., Piuzzi, N.S. (2022). Bone Marrow as a Source of Cells for Musculoskeletal Cellular Therapies. In: Filardo, G., Mandelbaum, B.R., Muschler, G.F., Rodeo, S.A., Nakamura, N. (eds) Orthobiologics. Springer, Cham. https://doi.org/10.1007/978-3-030-84744-9_2

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