Correction of coronary endothelial dysfunction is a possible accessory mechanism for cellular therapy of the heart

Abstract

SummaryOver 12 years of cellular therapy in cardiology, some dictinct positive results are obtained in randomized studies. However, exact mechanisms of hematopoietic stem cell actions are still unclear under these clinical conditions. Paracrine effects of cell therapy cannot explain all these effects. Enhanced neoangiogenesis upon stem cell injection is a proven mechanism for improvement of blood supply to the heart. Meanwhile, a decreased revascularization effect 3-4 years after cell therapy is followed by repeated myocardial improvement 6-9 mo after repeated cell infusions with active development of collateral vessels, thus suggesting an additional mechanism for improvement of coronary blood supply. Restoration of regulatory functions of endothelium and smooth muscle cells, including increased NO synthase activity of endothelium and its interactions with myocardiocytes may represent a probable mechanism for this action.

Assessment of safety of additional transplantation of autologous bone marrow mononuclear cells in the combined treatment of coronary heart disease. Results from a randomized, blind, placebo-controlled trial (TAMIS)

“…Но тем не менее однозначного ответа не получено. Именно поэтому, с учетом опыта использования АМНКМ в комплексной терапии па-циентов с различной кардиальной патологией [3][4][5][6][7][8] с 2003 года, было принято решение о проведении рандомизированного, слепого, плацебо контролируемого исследования. Работа получила международную регистрацию ClinicalTrials.gov, идентификационный номер NCT02059512 и проведена согласно утвержденному протоколу.…”

Does the local coronary endothelial dysfunction exist? Potential implications for cardiac cellular therapy

“…In such cases, a real eff ect of the cellular therapy should not exceed 3-6 months, and we cannot consider a solely cytokine eff ect. However, a long-term duration of a positive eff ect from cellular therapy with autologous freshly isolated bone marrow cells is as long as 3-4 years in most cases, thus suggesting a stem cell-mediated regeneration of some heart cell populations [25].…”

“…Today, however, basing on current results of cellular therapy performed in 250 patients over 15 years, one may presume that a local infusion of freshly isolated ABMC could exert favorable eff ects upon coronary blood fl ow and diminish clinical signs of heart insuffi ciency. Correction of endothelial dysfunction may be a suffi cient component of this mechanism [25].…”

“…Distinct improvement of myocardial perfusion, according to SPECT data, and better clinical condition (decreased CAD functional class) were noted in all four patients, who underwent repeated intracoronary ABMC injections. 6 to 12 months later, a second wave of improved myocardial perfusion was observed, according to consequent SPECT examinations with technetryl labeling [25].…”

Evaluation of the effectiveness of combined treatment of coronary heart disease – coronary artery bypass grafting, transplantation of autologous bone marrow mononuclear cells: a randomized, double-blind, placebo-controlled study

“…Данная работа была проведена после многолетних исследований в области клеточной/регенеративной медицины. Основой для разработки дизайна послужили ранее выполненные исследования в группах пациентов при лечении хронической ИБС, как изолированно, так и в сочетании с хирургическим лечением (ангиопластика и стентирование, АКШ), а также при лечении острого инфаркта миокарда (ОИМ) [19][20][21][22][23].…”