Intravenously Delivered Mesenchymal Stem Cells

Abstract

Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities.

Cortical Bone Stem Cells Administered at Reperfusion Attenuate Remote Zone Myocyte Remodeling

“…Thus, it seems plausible that the mechanism of action of CBSCs may actually reflect acute modulation of the host inflammatory response to myocardial injury in the ischemic as well as remote region of the heart. Further studies will be required to investigate this but similar immune modulatory actions have already been identified for CDCs 9 and MSCs 13 . The second relates to the time course of the functional improvement in CBSC-treated animals.…”

Cardiac Cell Therapy Evolving From Complex to Straightforward

“…These effects occurred in conjunction with a decrease in splenic pro-inflammatory Ly6C int /Ly6G hi neutrophils and modulation of T lymphocyte populations towards fewer natural killer cells, consistent with cardioprotective phenotype. 15 …”

Persistent Inflammation, Stem Cell–Induced Systemic Anti‐Inflammatory Effects, and Need for Repeated Stem Cell Injections: Critical Concepts Influencing Optimal Stem Cell Strategies for Treating Acute Myocardial Infarction and Heart Failure

“…For example, in the setting of AMI, there is a subgroup of patients whose progressive deterioration in left ventricular function is not caused solely by the AMI‐induced magnitude of myocardial damage, but involves other mechanisms 13. Chronic inflammation has been postulated as being one of these mechanisms responsible for progressive myocardial dysfunction in AMI, and also in HF 11, 12, 13, 14, 15

Systemic anti‐inflammatory effects of MSCs constitute one of the major mechanisms by which MSCs may improve left ventricular function.

Any myocardial benefit provided by stem cell administration is undoubtedly not caused by repopulating the damaged myocardium with new myocytes, but rather by paracrine activities with a diverse array of beneficial effects 12, 16, 17.

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“…For example, in the setting of AMI, there is a subgroup of patients whose progressive deterioration in left ventricular function is not caused solely by the AMI‐induced magnitude of myocardial damage, but involves other mechanisms 13. Chronic inflammation has been postulated as being one of these mechanisms responsible for progressive myocardial dysfunction in AMI, and also in HF 11, 12, 13, 14, 15…”

“…Prominent among these are marked systemic anti‐inflammatory effects, activities most firmly established for MSCs 12, 13, 15. These systemic anti‐inflammatory effects are induced by intravenous administration of MSCs and constitute an important mechanism by which MSCs improve myocardial function in murine models of AMI and ischemic cardiomyopathy 15.…”