The Journal of Bone and Joint Surgery (American). 2008;90:2390-2398.
doi:10.2106/JBJS.H.00049
© 2008 The Journal of Bone and Joint Surgery, Inc.
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Differentiation Potential of Multipotent Progenitor Cells Derived from War-Traumatized Muscle Tissue

Major Leon J. Nesti, MD, PhD1, Wesley M. Jackson, PhD2, Rabie M. Shanti, BA2, Steven M. Koehler, BA2, Captain Amber B. Aragon, MD2, Ensign James R. Bailey, BA3, Ensign Michael K. Sracic, BA3, Major Brett A. Freedman, MD4, Captain Jeffrey R. Giuliani, MD2 and Rocky S. Tuan, PhD2

1 6900 Georgia Avenue NW, Building 2, Room 5B28, Washington, DC 20307. E-mail address: leonnesti{at}gmail.com
2 Cartilage Biology and Orthopaedic Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, 50 South Drive, Room 1100, Bethesda, MD 20892
3 Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814
4 Integrated Department of Orthopaedics and Rehabilitation, Walter Reed Army Medical Center, Washington, DC

Investigation performed at the Cartilage Biology and Orthopaedic Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, and Walter Reed Army Medical Center, Washington, DC

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the Military Amputee Research Program at Walter Reed Army Medical Center (PO5-A011) and by the Intramural Research Program at the NIH, NIAMS (Z01 AR41131). Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

Background: Recent military conflicts have resulted in numerous extremity injuries requiring complex orthopaedic reconstructive procedures, which begin with a thorough débridement of all contaminated and necrotic tissue in the zone of injury. The site of injury is also the site of healing, and we propose that débrided muscle tissue contains cells with robust reparative and regenerative potential.

Methods: Débrided muscle from soldiers who had sustained traumatic open extremity injuries was collected during surgical débridement procedures at Walter Reed Army Medical Center. With modifications to a previously described stem-cell-isolation protocol, mesenchymal progenitor cells were harvested from traumatized muscle, enriched, expanded in culture, and exposed to induction media for osteogenesis, adipogenesis, and chondrogenesis.

Results: The isolated mesenchymal progenitor cells stained positive for cell-surface markers (CD73, CD90, CD105), which are characteristic of adult human mesenchymal stem cells. Histological identification of lineage-specific markers demonstrated the potential of these cells to differentiate into multiple mesenchymal lineages. Reverse transcription-polymerase chain reaction analysis confirmed multilineage mesenchymal differentiation at the gene-expression level.

Conclusions: To our knowledge, the present report provides the first description of mesenchymal progenitor cell isolation from traumatized human muscle. These cells may play an integral role in tissue repair and regeneration and merit additional investigation as they could be useful in future cell-based tissue-engineering strategies.

Clinical Significance: Mesenchymal progenitor cells isolated from war-traumatized tissues have the potential for applications in cell-based tissue engineering. Elucidating the cellular mechanisms regulating their differentiation activities may lead to the development of novel treatments for musculoskeletal trauma and pathological healing responses, such as heterotopic ossification.


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