Menstrual Blood-derived Cells Confer Human Dystrophin Expression in the Murine Model of Duchenne Muscular Dystrophy via Cell Fusion and Myogenic Transdifferentiation

Abstract

Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder in children, is an X-linked recessive muscle disease characterized by the absence of dystrophin at the sarcolemma of muscle fibers. We examined a putative endometrial progenitor obtained from endometrial tissue samples to determine whether these cells repair muscular degeneration in a murine mdx model of DMD. Implanted cells conferred human dystrophin in degenerated muscle of immunodeficient mdx mice. We then examined menstrual blood-derived cells to determine whether primarily cultured nontransformed cells also repair dystrophied muscle. In vivo transfer of menstrual blood-derived cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of dystrophin. Labeling of implanted cells with enhanced green fluorescent protein and differential staining of human and murine nuclei suggest that human dystrophin expression is due to cell fusion between host myocytes and implanted cells. In vitro analysis revealed that endometrial progenitor cells and menstrual blood-derived cells can efficiently transdifferentiate into myoblasts/myocytes, fuse to C2C12 murine myoblasts by in vitro coculturing, and start to express dystrophin after fusion. These results demonstrate that the endometrial progenitor cells and menstrual blood-derived cells can transfer dystrophin into dystrophied myocytes through cell fusion and transdifferentiation in vitro and in vivo.

Noncanonical NOTCH Signaling Limits Self-Renewal of Human Epithelial and Induced Pluripotent Stem Cells through ROCK Activation

“…All experiments involving human cells and tissues were performed in line with Tenets of the Declaration of Helsinki. Human iPS cell lines, MRC-hiPSCs and UtE-hiPSCs, were established from MRC-5 fetal lung fibroblasts (43) and UtE1104 endometrium-derived cells (44), respectively, via procedures described by Takahashi et al (45) with slight modification (46,47). Human iPS cells were maintained in iPSellon medium (Cardio Incorporated, Osaka, Japan) supplemented with 10 ng/ml recombinant human basic fibroblast growth factor (bFGF) (Wako Pure Chemical Industries, Ltd., Osaka, Japan) in the presence of irradiated mouse embryonic fibroblast (MEF) feeders.…”

Haid daripada Perspektif Sains dan Maqasid Syariah

“…Walau bagaimanapun, mendapatkan sel-sel secara langsung akan menjadi prosedur yang sangat sukar. Cara alternatif adalah daripada darah haid yang mengandungi darah dan tisu yang luruh daripada endometrium yang mengandungi satu populasi sel yang heterogenus yang berupaya untuk tumbuh semula (Cui et al 2007). Sel rahim stromal mempunyai penanda multipoten sama yang biasa dijumpai di dalam sum-sum tulang (Kearns & Lala;Schwab & Gargett 2007;Taylor 2004).…”

Myogenic Properties of Human Mesenchymal Stem Cells Derived from Three Different Sources

“…In freshly isolated BM cell preparations, the The myogenic propensity of human MSCs of the three sources has been individually investigated by others on CD200 + cell fraction was highly enriched for cells with MSC properties (24). The only available data on culthe basis of myogenic gene expression profile and fusion capacity (15,22,25,54,72,88). Single-cell microarray tured MSCs is from BM-derived cells, which were shown to down regulate this marker upon culture (5).…”

“…An example is the response of MSCs to the demethylating agent 5-MSCs were isolated from AT, BM, and SM of three patients (donor 1: male, 65 years old; donor 2: male, 69 azacytidine. Exposure of MSCs derived from rat BM (82), human menstrual blood (15), or human SM (21) to years old; donor 3: female, 72 years old). Samples were surgical waste collected with informed consent during 5-azacytidine during culture stimulates myotube formation and the expression of skeletal muscle-specific markorthopedic surgery and according to the guidelines of the Leiden University Medical Center (LUMC; Leiden, ers.…”