Transplanted Skeletal Myoblasts Can Fully Replace the Infarcted Myocardium When They Survive in the Host in Large Numbers

Tambara, Keiichi; Sakakibara, Yutaka; Sakaguchi, Genichi; Lu, Fanglin; Premaratne, Goditha U.; Xue, Liyan; Nishimura, Kazunobu; Komeda, Masashi

doi:10.1161/01.cir.0000087430.17543.b8

Cited by 87 publications

(93 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At 4 days after injury mononucleated cells (inflammatory cells and myoblasts) increase in number, and appearance of new myotubes is observed for left and right TA muscles (4d R and 4d L). ·100 magnification was inhibited [62]. The use of fetal cells may bypass these inconveniences.…”

Section: Discussionmentioning

confidence: 99%

“…Up to 90% of these cell types have been reported to be killed over the first 48 h following their implantation [24,25]. This major loss of grafted cells is likely to seriously hamper the efficacy of the procedure, as the functional benefit expected from myoblast transplantation seems closely related to the number of injected myoblasts [26]. Efforts have been made to improve cell survival, either by changing immunosuppressive or anti-inflammatory agents [27][28][29], changing the cell source [30] and pretreatment of cells [31] or by improving purification of specific cells populations [32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Human muscular fetal cells: a potential cell source for muscular therapies

Hirt‐Burri¹,

Roessingh²,

Scaletta

et al. 2007

Pediatr Surg Int

View full text Add to dashboard Cite

Myoblast transfer therapy has been extensively studied for a wide range of clinical applications, such as tissue engineering for muscular loss, cardiac surgery or Duchenne Muscular Dystrophy treatment. However, this approach has been hindered by numerous limitations, including early myoblast death after injection and specific immune response after transplantation with allogenic cells. Different cell sources have been analyzed to overcome some of these limitations. The object of our study was to investigate the growth potential, characterization and integration in vivo of human primary fetal skeletal muscle cells. These data together show the potential for the creation of a cell bank to be used as a cell source for muscle cell therapy and tissue engineering. For this purpose, we developed primary muscular cell cultures from biopsies of human male thigh muscle from a 16-week-old fetus and from donors of 13 and 30 years old. We show that fetal myogenic cells can be successfully isolated and expanded in vitro from human fetal muscle biopsies, and that fetal cells have higher growth capacities when compared to young and adult cells. We confirm lineage specificity by comparing fetal muscle cells to fetal skin and bone cells in vitro by immunohistochemistry with desmin and 5.1H11 antibodies. For the feasibility of the cell bank, we ensured that fetal muscle cells retained intrinsic characteristics after 5 years cryopreservation. Finally, human fetal muscle cells marked with PKH26 were injected in normal C57BL/6 mice and were found to be present up to 4 days. In conclusion we estimate that a human fetal skeletal muscle cell bank can be created for potential muscle cell therapy and tissue engineering.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human muscular fetal cells: a potential cell source for muscular therapies

Hirt‐Burri¹,

Roessingh²,

Scaletta

et al. 2007

Pediatr Surg Int

View full text Add to dashboard Cite

show abstract

“…Indeed, studies in skeletal myoblast transplantation indicate that graft size is directly correlated with functional improvement [34,35]. A few calculations are helpful in assessing the scope of regenerating a human myocardial infarct.…”

Section: Introductionmentioning

confidence: 99%

Systems approaches to preventing transplanted cell death in cardiac repair

Robey

Saiget

Reinecke

et al. 2008

Journal of Molecular and Cellular Cardiology

360

290

View full text Add to dashboard Cite

Stem cell transplantation may repair the injured heart, but tissue regeneration is limited by death of transplanted cells. Most cell death occurs in the first few days post-transplantation, likely from a combination of ischemia, anoikis and inflammation. Interventions known to enhance transplanted cell survival include heat shock, over-expressing anti-apoptotic proteins, free radical scavengers, anti-inflammatory therapy and co-delivery of extracellular matrix molecules. Combinatorial use of such interventions markedly enhances graft cell survival, but death still remains a significant problem. We review these challenges to cardiac cell transplantation and present an approach to systematically address them.Most anti-death studies use histology to assess engraftment, which is time-and labor-intensive. To increase throughput, we developed two biochemical approaches to follow graft viability in the mouse heart. The first relies on LacZ enyzmatic activity to track genetically modified cells, and the second quantifies human genomic DNA content using repetitive Alu sequences. Both show linear relationships between input cell number and biochemical signal, but require correction for the time lag between cell death and loss of signal. Once optimized, they permit detection of as few as 1 graft cell in 40,000 host cells. Pro-survival effects measured biochemically at three days predict long-term histological engraftment benefits. These methods permitted identification of carbamylated erythropoietin (CEPO) as a pro-survival factor for human embryonic stem cell-derived cardiomyocyte grafts. CEPO's effects were additive to heat shock, implying independent survival pathways. This system should permit combinatorial approaches to enhance graft viability in a fraction of the time required for conventional histology.

show abstract

“…Many studies, including ours, [1][2][3] have demonstrated favorable results in animal experiments, and several clinical trials are now underway with promising outcomes. [4][5][6][7] Although skeletal myoblasts (SMs) are favored as donor cells for transplantation, there is no clear evidence that SMs transdifferentiate into cardiomyocytes, and ventricular arrhythmia may be a major drawback with this cell source in human applications.…”

mentioning

confidence: 87%

Delivery Route in Bone Marrow Cell Transplantation Should be Optimized According to the Etiology of Heart Disease

Nakajima

Sakakibara

Tambara

et al. 2008

Circ J

Self Cite

View full text Add to dashboard Cite

Preparation of BMCsBMCs were harvested from 8-week-old syngenic and transgenic male C57Bl/6 mice expressing enhanced green fluorescent protein (GFP), by flushing the femurs and tibias Circ J 2008; 72: 1528 -1535 (Received August 23, 2006 revised manuscript received April 28, 2008; accepted May 9, 2008 Background Recent studies have revealed that bone marrow cell (BMC) transplantation is effective not only for myocardial infarction (MI), but also for dilated cardiomyopathy (DCM). However, the method of administering donor cells remains unknown, and may differ between MI and DCM. In the present study, intramyocardial (IM) injection and intravenous (IV) delivery of BMC were compared in each etiological model. Methods and Results MI was induced in 72 mice and DCM in another 36 mice by doxorubicin. BMCs were administered IV or IM in an acute MI (AMI), old MI (OMI) or DCM model. In the AMI model, left ventricular (LV) remodeling was reduced in both the IM-and IV-groups, but only in the IM-group in the OMI model. In the DCM model, the LV dimension of the IV-group was smaller than that of the IM-group. Histological examination showed that green fluorescent protein (GFP) cells were equally distributed in the infarct area of the IV-and IMgroups in AMI, and in the IM-group in the OMI model. In the DCM model, GFP cells were diffusely scattered throughout the ventricular wall in the IV-group, but were confined to the injection site in the IM-group. Conclusions In OMI, IM delivery of BMCs was more effective than IV; however, IV delivery was superior in DCM. Delivery route should be selected according to the etiology of heart disease to optimize the efficacy of BMC transplantation. (Circ J 2008; 72: 1528 -1535

show abstract

Transplanted Skeletal Myoblasts Can Fully Replace the Infarcted Myocardium When They Survive in the Host in Large Numbers

Cited by 87 publications

References 18 publications

Human muscular fetal cells: a potential cell source for muscular therapies

Human muscular fetal cells: a potential cell source for muscular therapies

Systems approaches to preventing transplanted cell death in cardiac repair

Delivery Route in Bone Marrow Cell Transplantation Should be Optimized According to the Etiology of Heart Disease

Contact Info

Product

Resources

About