Placental Perivascular Cells for Human Muscle Regeneration

Tea Park

Manuela Gavina

Chien Chen

Bin Sun

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^{Stem Cell Research Center, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.}

^{Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, Maryland.}

^{McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.}

^{Department of Orthopedic Surgery, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.}

^{Orthopaedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.}

^{Corresponding author.}

Address correspondence to: Prof. Bruno Péault, Orthopaedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, 615 Charles E. Young Drive South, Los Angeles, CA 90095-7358. E-mail:ude.alcu.tendem@tluaepb

^{There authors equally contributed to this work.}

Received 2010 Aug 20; Accepted 2010 Oct 5.

Abstract

Perivascular multipotent mesenchymal progenitors exist in a variety of tissues, including the placenta. Here, we suggest that the abundant vasculature present in the human placenta can serve as a source of myogenic cells to regenerate skeletal muscle. Chorionic villi dissected from the mid-gestation human placenta were first transplanted intact into the gastrocnemius muscles of SCID/mdx mice, where they participated in muscle regeneration by producing myofibers expressing human dystrophin and spectrin. In vitro-cultured placental villi released rapidly adhering and migratory CD146+CD34−CD45−CD56− cells of putative perivascular origin that expressed mesenchymal stem cell markers. CD146+CD34−CD45−CD56− perivascular cells isolated and purified from the placental villi by flow cytometry were indeed highly myogenic in culture, and generated dystrophin-positive myofibers, and they promoted angiogenesis after transplantation into SCID/mdx mouse muscles. These observations confirm the existence of mesenchymal progenitor cells within the walls of human blood vessels, and suggest that the richly vascularized human placenta is an abundant source of perivascular myogenic cells able to migrate within dystrophic muscle and regenerate myofibers.

Abstract

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