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【medical-news】移植人体非特异性干细胞以提高急
Heart 2009;95:27-35
Objective: Functional improvement after acute myocardial ischaemia (MI) has been achieved by transplantation of different adult stem and progenitor cell types. It is controversial whether these cell types are able to form novel functional myocardium. Alternatively, graft-related or immune-related paracrine mechanisms may preserve existing myocardium, improve neovascularisation, affect tissue remodelling or induce endogenous de novo formation of functional myocardium. We have applied an alternative somatic cell type, human cord-blood-derived unrestricted somatic stem cells (USSCs) in a porcine model of acute MI.
Methods: USSCs were transplanted into the acutely ischaemic lateral wall of the left ventricle (LV). LV dimension and function were assessed by transoesophageal echocardiography (TEE) pre-MI, immediately post-MI, 48 hours and 8 weeks after USSC injection. Additionally, apoptosis, mitosis and recruitment of macrophages were examined 48 hours post-engraftment.
Results: Gender-specific and species-specific FISH/immunostaining failed to detect engrafted donor cells 8 weeks post-MI. Nevertheless, cell treatment effectively preserved natural myocardial architecture. Global left ventricular ejection fraction (LVEF) before MI was 60% (7%). Post-MI, LVEF decreased to 34% (8%). After 8 weeks, LVEF had further decreased to 27% (6%) in the control group and recovered to 52% (2%) in the USSC group (p<0.01). Left-ventricular end-diastolic volume (LVEDV) before MI was 28 (2) ml. 8 weeks post-MI, LVEDV had increased to 77 (4) ml in the control group. No LV dilation was detected in the USSC group (LVEDV: 26 (2) ml, p<0.01). Neither apoptosis nor recruitment of macrophages and mitosis were different in either groups.
Conclusions: Transplantation of USSCs significantly improved LV function and prevented scar formation as well as LV dilation. Since differentiation, apoptosis and macrophage mobilisation at infarct site were excluded as underlying mechanisms, paracrine effects are most likely to account for the observed effects of USSC treatment.
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While cell therapy is emerging as a possible therapeutic option for cardiac regeneration, identification of the optimal cell source remains imperative for clinical cardiomyoplasty. In contrast to embryonic stem cells, which are doubtless able to generate functional cardiomyocytes, previous findings,1–8 demonstrating cardiogenic potential of extracardiac somatic stem and progenitor cells, and especially bone marrow derived cells, are controversial. Although over the past years evidence accumulated that after transplantation or cytokine-induced mobilisation of bone marrow cells (BMC), a certain percentage of those cells contribute to de novo formation of myocytes,4 5 7 a series of critical studies raised doubt on the ability of those cells to generate functional cardiomyocytes.9–13 According to those studies, de novo generation of cardiomyocytes from extracardiac somatic stem and progenitor cells does not occur or appears to be an extremely rare event without major impact for myocardial regeneration.
Nevertheless, a series of small and large animal studies as well as clinical studies demonstrated functional improvement after myocardial transplantation of somatic stem and progenitor cells.4 5 14–19 Identification of the underlying mechanisms might lead to novel therapeutic strategies especially for treatment of acute myocardial infarction. Those mechanisms probably include paracrine pathways resulting in prevention of apoptosis and enhanced neovascularisation of ischaemic myocardium as well as induction of endogenous de novo formation of myocardium and altered tissue remodelling.20–22
Human unrestricted somatic stem cells (USSC) are a newly discovered cell type with relatively low immunogenicity, which can be isolated from cord blood. USSCs display higher levels of pluripotency and higher expansion potential than most adult stem and progenitor cells.23 Notably, USSCs release a multitude of cytokines.24 With regard to the manifold cytokine release, we aimed to assess whether intramyocardial transfer of USSCs immediately after acute ischaemia can support recovery of global left-ventricular ejection fraction (LVEF) and prevent LV dilation in a porcine model. [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-02-25 05:11
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