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Abstract
AIM. As the capability of human mesenchymal stem cells (hMSC) to engraft, differentiate and improve myocardial function cannot be studied in humans, exploration was performed in a xenomodel.
METHODS. The rats were divided into three groups depending on the type of rats used (Rowett nude (RNU) or Fischer rats +/− immunosuppression). Different groups were treated with intramyocardial injection of hMSC (1–2 million) either directly or three days after ligation of the left anterior descending artery (LAD). Myocardial function was investigated by echocardiography. The hMSC were identified with fluorescence in situ hybridization and myocardial differentiation was assessed by immunohistochemistry.
RESULTS. When hMSC were injected directly after LAD ligation they could be identified in half (8/16) of the RNU rats (without immunosuppression) at 4 weeks. When injected 3 days after LAD ligation in immunosuppressed RNU rats they were identified in all (6/6) rats at 6 weeks. The surviving hMSC showed signs of differentiation into fibroblasts. No cardiomyocyte differentiation was observed. There was no difference in myocardial function in treated animals compared to controls.
CONCLUSIONS. The hMSC survived in this xenomodel up to 6 weeks. However, hMSC required implantation into immunoincompetent animals as well as immunosuppression to survive, indicating that these cells are otherwise rejected. Furthermore, these cells did not differentiate into cardiomyocytes nor did they improve heart function in this xenomodel.
| Abbreviations | ||
| hMSC | = | human mesenchymal stem cells |
| ES | = | embryonic stem cells |
| RNU | = | Rowett nude rats: athymic rats with the genotype rnu/rnu |
| LAD | = | left anterior descending artery |
| FISH | = | fluorescent in situ hybridization technique |
| GFP | = | green fluorescent protein |
| LVEDD | = | left ventricular end diastolic dimension |
| FAC | = | fractional area change |
| MO | = | magnet‐optic disc |
| SSC | = | sodium citrate‐sodium chloride buffer |
| PBS | = | phosphate‐buffered saline solution |
| DAPI | = | 4′, 6‐diamidino‐2‐phenylindole |
| FITC | = | fluorescein isothiocyanate |
| IFN‐γ | = | interferon‐γ |
| IL‐10 | = | interleukin‐10 |
| PGE2 | = | prostaglandin E2 |
| NK | = | natural killer cells |
| Abbreviations | ||
| hMSC | = | human mesenchymal stem cells |
| ES | = | embryonic stem cells |
| RNU | = | Rowett nude rats: athymic rats with the genotype rnu/rnu |
| LAD | = | left anterior descending artery |
| FISH | = | fluorescent in situ hybridization technique |
| GFP | = | green fluorescent protein |
| LVEDD | = | left ventricular end diastolic dimension |
| FAC | = | fractional area change |
| MO | = | magnet‐optic disc |
| SSC | = | sodium citrate‐sodium chloride buffer |
| PBS | = | phosphate‐buffered saline solution |
| DAPI | = | 4′, 6‐diamidino‐2‐phenylindole |
| FITC | = | fluorescein isothiocyanate |
| IFN‐γ | = | interferon‐γ |
| IL‐10 | = | interleukin‐10 |
| PGE2 | = | prostaglandin E2 |
| NK | = | natural killer cells |
Acknowledgments
The Swedish Medical Research Council (9515), the Swedish Heart and Lung Foundation, the Belvén Foundation, the Tobias Foundation, the Tore Nilsson Foundation, the Swedish Cancer Society (4562‐B03‐XAC), the Children's Cancer Foundation (01/039), the Swedish Research Council (K2003‐32XD‐14716‐01A), the Stockholm Cancer Society, the Swedish Medical Society and the Karolinska Institutet supported this study.