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Assessing the Resident Progenitor Cell Population and the Vascularity of the Adult Human Meniscus

  • Author Footnotes
    ∗ Jorge Chahla and Angela Papalamprou contributed equally to this study and are considered as co-first authors.
    Jorge Chahla
    Footnotes
    ∗ Jorge Chahla and Angela Papalamprou contributed equally to this study and are considered as co-first authors.
    Affiliations
    Kerlan Jobe Institute, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
    Search for articles by this author
  • Author Footnotes
    ∗ Jorge Chahla and Angela Papalamprou contributed equally to this study and are considered as co-first authors.
    Angela Papalamprou
    Footnotes
    ∗ Jorge Chahla and Angela Papalamprou contributed equally to this study and are considered as co-first authors.
    Affiliations
    Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
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  • Virginia Chan
    Affiliations
    Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
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  • Yasaman Arabi
    Affiliations
    Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
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  • Khosrawdad Salehi
    Affiliations
    Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
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  • Trevor J. Nelson
    Affiliations
    Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
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  • Orr Limpisvasti
    Affiliations
    Kerlan Jobe Institute, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
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  • Bert R. Mandelbaum
    Affiliations
    Kerlan Jobe Institute, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
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  • Wafa Tawackoli
    Affiliations
    Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
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  • Melodie F. Metzger
    Affiliations
    Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
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  • Dmitriy Sheyn
    Correspondence
    Address correspondence to Dmitriy Sheyn, Ph.D., Orthopedic Stem Cell Research Lab, Board of Governors Regenerative Medicine Institute, Department of Orthopedics, Department of Surgery, Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, AHSP A8308, Los Angeles, CA 90048.
    Affiliations
    Kerlan Jobe Institute, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.

    Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, U.S.A.
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  • Author Footnotes
    ∗ Jorge Chahla and Angela Papalamprou contributed equally to this study and are considered as co-first authors.
Published:September 23, 2020DOI:https://doi.org/10.1016/j.arthro.2020.09.021

      Purpose

      To identify, characterize, and compare the resident progenitor cell populations within the red−red, red−white, and white−white (WW) zones of freshly harvested human cadaver menisci and to characterize the vascularity of human menisci using immunofluorescence and 3-dimensional (3D) imaging.

      Methods

      Fresh adult human menisci were harvested from healthy donors. Menisci were enzymatically digested, mononuclear cells isolated, and characterized using flow cytometry with antibodies against mesenchymal stem cell surface markers (CD105, CD90, CD44, and CD29). Cells were expanded in culture, characterized, and compared with bone marrow−derived mesenchymal stem cells. Trilineage differentiation potential of cultured cells was determined. Vasculature of menisci was mapped in 3D using a modified uDisco clearing and immunofluorescence against vascular markers CD31, lectin, and alpha smooth muscle actin.

      Results

      There were no significant differences in the clonogenicity of isolated cells between the 3 zones. Flow cytometry showed presence of CD44+CD105+CD29+CD90+ cells in all 3 zones with high prevalence in the WW zone. Progenitors from all zones were found to be potent to differentiate to mesenchymal lineages. Larger vessels in the red−red zone of meniscus were observed spanning toward red−white, sprouting to smaller arterioles and venules. CD31+ cells were identified in all zones using the 3D imaging and co-localization of additional markers of vasculature (lectin and alpha smooth muscle actin) was observed.

      Conclusions

      The presence of resident mesenchymal progenitors was evident in all 3 meniscal zones of healthy adult donors without injury. In addition, our results demonstrate the presence of vascularization in the WW zone.

      Clinical Relevance

      The existence of progenitors and presence of microvasculature in the WW zone of the meniscus suggests the potential for repair and biologic augmentation strategies in that zone of the meniscus in young healthy adults. Further research is necessary to fully define the functionality of the meniscal blood supply and its implications for repair.
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