Comparison of Bone Marrow Aspirate Concentrate and Allogenic Human Umbilical Cord Blood Derived Mesenchymal Stem Cell Implantation on Chondral Defect of Knee: Assessment of Clinical and Magnetic Resonance Imaging Outcomes at 2-Year Follow-Up

Ryu, Dong Jin; Jeon, Young-Chan; Park, Joon Seong; Bae, Gi Cheol; Kim, Jeong‐Seok; Kim, Myung Ku

doi:10.1177/0963689720943581

Cited by 30 publications

(33 citation statements)

References 49 publications

(84 reference statements)

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“… 1 , 14 Because of the small number of MSCs per unit volume of aspiration, BMAC has been considered as a method to increase the concentration of MSCs in a short time, directly in the operating room. 28 – 32 BMAC involves using a density gradient centrifuge in order to concentrate MSCs, and many kits are available. 18 , 28 However, there are conflicting findings regarding the superiority of BMAC over traditional BMA.…”

Section: Discussionmentioning

confidence: 99%

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High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique

Brozovich

Sinicrope

Bauza

et al. 2021

Orthopaedic Journal of Sports Medicine

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Background: Bone marrow aspirate (BMA) is a common source for harvesting mesenchymal stem cells (MSCs), other progenitor cells, and associated cytokines and growth factors to be used in the biologic treatment of various orthopaedic pathologies. The aspirate is commonly centrifuged into a concentrated volume that can be immediately administered to a patient using commercially available kits. However, the handling and efficacy of BMA concentrate (BMAC) are still controversial. Purpose: To characterize BMA versus BMAC for MSC quantity, potency, and cytokine profile. Study Design: Controlled laboratory study. Methods: From 8 participants (age, 17-68 years), 30 mL of bone marrow was aspirated by a single surgeon from either the proximal humerus or distal femur and was separated into 2 equal samples. One sample was kept as BMA, and the other half was centrifuged into BMAC. The 2 samples then underwent flow cytometry for detection of MSCs, cell analysis for colony-forming units (CFUs), and cytokine profiling. A 2-tailed t test was used to detect differences between MSCs, CFUs, and cytokine density concentrations between BMA and BMAC. Results: The average concentration of MSCs in both BMA and BMAC was 0.001%. Average MSC events detected by flow cytometry were significantly higher in BMA versus BMAC (15.1 and 8.1, respectively; P < .045). Expanded MSCs demonstrated similar phenotypes, but CFUs were significantly increased in BMA compared with BMAC (104 vs 68 CFUs, respectively; P < .001). Total protein concentration and cytokine profiling demonstrated great variability between BMA and BMAC and between patients. Most importantly, BMAC failed to concentrate MSCs in 6 of 8 samples. Conclusion: There is great variability in MSC concentration, total protein concentration, and cytokine profile between BMA and BMAC. Clinical Relevance: When studying the clinical efficacy of BMAC, one must also evaluate the sample itself to determine the presence, concentration, and potency of MSCs if this is to be considered a cell-based therapy. Further standard operating procedures need to be investigated to ensure reproducible results and appropriate treatments.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, often the use of BMA or BMAC in orthopaedic procedures has been improperly defined or advertised as stem cell therapy to render it more appealing. 12 , 13 , 18 , 19 , 25 , 28 , 31 …”

mentioning

confidence: 99%

High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique

Brozovich

Sinicrope

Bauza

et al. 2021

Orthopaedic Journal of Sports Medicine

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“…Compared to ADSCs, a mixture of ADSCs, EPCs, and lymphocytes among other cell types (i.e., SVF) has received more praise in preclinical comparative studies, in part due to the heterogeneity of cellular composition perceived to exploit more physiologic properties (e.g., angiogenesis, immunomodulation, cellular differentiation) that collectively drive better outcomes (332)(333)(334)(335). Notable, the first study to compare MSCs vs. BMAC (i.e., MSCs, progenitor cells, white blood cells, etc...) on the scale of clinical and magnetic resonance imaging (MRI) outcomes in 52 patients with chondral knee defects has found no differences in retrospect between both treatments over a 2 year follow-up (336). Similarly, a recent retrospective study found no differences in postoperative radiological findings and pain/functionality outcomes in patients who underwent high tibial osteotomy with microfracture combined with either MSCs or BMAC for medial unicompartmental knee OA (337).…”

Section: Multicellular Vs Unicellular Therapiesmentioning

confidence: 99%

Cell Therapy: Types, Regulation, and Clinical Benefits

2021

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Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non–stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review article, we delineate the vast types of cell therapy, including stem cell-based and non–stem cell-based cell therapies, and create the first-in-literature compilation of the different “multicellular” therapies used in clinical settings. Besides providing the nuts and bolts of FDA policies regulating their use, we discuss the benefits of cell therapies reported in 3 therapeutic areas—regenerative medicine, immune diseases, and cancer. Finally, we contemplate the recent attention shift toward combined therapy approaches, highlighting the factors that render multicellular therapies a more attractive option than their unicellular counterparts.

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“… Notes : Many recent studies have evaluated allogeneic UC‐MSCs, 94 , 95 , 96 , 97 , 98 , 99 , 100 although there are many variations in dose, mode of application, the use in conjunction with surgical intervention, and addition of adjunctive therapeutic agents such as hyaluronic acid and somatotropin. Other cell sources, AD‐MSCs, BM‐MSCs, and synovial derived MSCs, continue to deliver promising results.…”

Section: Efficacy Of Recent Clinical Trials Utilizing Culture Expanded Allogeneic and Autologous Mscsmentioning

confidence: 99%

Allogeneic Mesenchymal Stromal Cells for Cartilage Regeneration: A Review of in Vitro Evaluation, Clinical Experience, and Translational Opportunities

Aldrich

Cui

Murphy

et al. 2021

Stem Cells Translational Medicine

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The paracrine signaling, immunogenic properties and possible applications of mesenchymal stromal cells (MSCs) for cartilage tissue engineering and regenerative medicine therapies have been investigated through numerous in vitro, animal model and clinical studies. The emerging knowledge largely supports the concept of MSCs as signaling and modulatory cells, exerting their influence through trophic and immune mediation rather than as a cell replacement therapy. The virtues of allogeneic cells as a ready-to-use product with well-defined characteristics of cell surface marker expression, proliferative ability, and differentiation capacity are well established. With clinical applications in mind, a greater focus on allogeneic cell sources is evident, and this review summarizes the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and the role of trophic factors in articular chondrocyte-MSC interactions that offer feasible targets for evaluating MSC activity in vivo within the intra-articular environment. Furthermore, bringing labeling and tracking techniques to the clinical setting, while inherently challenging, will be extremely informative as clinicians and researchers seek to bolster the case for the safety and efficacy of allogeneic MSCs. We therefore review multiple promising approaches for cell tracking and labeling, including both chimerism studies and imaging-based techniques, that have been widely explored in vitro and in animal models. Understanding the distribution and persistence of transplanted MSCs is necessary to fully realize their potential in cartilage regeneration techniques and tissue engineering applications.

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Comparison of Bone Marrow Aspirate Concentrate and Allogenic Human Umbilical Cord Blood Derived Mesenchymal Stem Cell Implantation on Chondral Defect of Knee: Assessment of Clinical and Magnetic Resonance Imaging Outcomes at 2-Year Follow-Up

Cited by 30 publications

References 49 publications

High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique

High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique

Cell Therapy: Types, Regulation, and Clinical Benefits

Allogeneic Mesenchymal Stromal Cells for Cartilage Regeneration: A Review of in Vitro Evaluation, Clinical Experience, and Translational Opportunities

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