Effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia

Abstract

Purpose:To evaluate the effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia. Materials and Methods:In 24 patients (19 male; 65 Ϯ 9 years) with refractory angina (Canadian Cardiovascular Society [CCS] class III-IV) 84.6 Ϯ 28.7 ϫ 10 6 bone marrowderived mononuclear cells were injected intramyocardially (using the NOGA system) in regions with ischemia on Tc99m tetrofosmin single photon emission computed tomography (SPECT). Diastolic function was evaluated at baseline and at three months using magnetic resonance imaging (MRI) and tissue Doppler imaging (TDI).Results: MRI revealed an increased early (E) peak filling rate (374 Ϯ 121 mL/second vs. 412 Ϯ 102 mL/second; P ϭ 0.04), whereas the atrial (A) peak filling rate remained unchanged (340 Ϯ 81 mL/second vs. 334 Ϯ 93 mL/second; P ϭ not significant [NS]). The E/A peak flow ratio increased from 1.09 Ϯ 0.33 to 1.23 Ϯ 0.47 at three months (P ϭ 0.02). TDI demonstrated a significant improvement in early diastolic velocity (EЈ) from 4.4 Ϯ 1.7 cm/second to 4.8 Ϯ 1.6 cm/second at three months (P ϭ 0.03), whereas the late diastolic velocity (AЈ) remained unchanged (6.0 Ϯ 1.6 cm/ second vs. 6.0 Ϯ 1.7 cm/second; P ϭ NS). Consequently, the EЈ/AЈ ratio increased from 0.74 Ϯ 0.19 to 0.84 Ϯ 0.28 at three months (P ϭ 0.02). Conclusion:Intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia improved MRI and TDI-derived parameters of diastolic function.

Intramyocardial Bone Marrow–Derived Mononuclear Cell Injection for Chronic Myocardial Ischemia

“…Furthermore, in a nonrandomized clinical study from our group in patients with chronic myocardial ischemia, improved myocardial relaxation was observed after intramyocardial bone marrow cell injection. 8 The current study is the first to confirm the beneficial effect of intramyocardial bone marrow cell injection on diastolic function in a randomized, double-blinded, placebo-controlled clinical trial in patients with chronic myocardial ischemia. In the present study, the E/EЈ ratio was chosen as a primary end point of the study because this parameter has been shown to provide a reliable estimate of LV filling pressures.…”

“…8 On the basis of these results, the current substudy was conducted to investigate the effect of intramyocardial bone marrow cell injection on LV diastolic function in a randomized, double-blinded, placebo-controlled setting. Diastolic function was evaluated by echocardiographic measurement of parameters of filling pressure, myocardial relaxation, and ventricular compliance with the use of tissue Doppler imaging (TDI) and speckle-tracking strain analysis.…”

Myocardial therapeutic angiogenesis: a review of the state of development and future obstacles

“…While circulating EPCs likely contribute to vasculogenesis, most interest is now in directed delivery of large numbers of cells to induce therapeutic vasculogenesis [67]. Early phase clinical trials have shown some benefit, improved exercise capacity and ventricular function in patients with ischemic heart disease [68,69]. However, like MSCs, there is controversy over the actual role of the transplanted cells in neovascularization [70].…”

Stem Cells Therapy in General Medicine

“…There are differences in usage of MSCs in clinical applications. The majority reports use bone marrow-derived MSCs (BM-MSCs) which are expanded in vitro before in vivo applications (15,16), whereas other reports show where they used stem cells bypassing selection step in animal and human studies (17)(18)(19) and there are studies where stem cells were selected by using surface markers prior to use (20,21). In vitro expansion of stem cells prior injection can reduce the quality of treatment, because of the prolonged culturing period and limited functional potential (22).…”

“…Besides, there are no currently available reports showing the optimal dosage and route of administration of stem cells neither in human nor in animal models. Nevertheless, the most common route of interventions conducted via intraarterial or intravenous infusions to provide systemic delivery to damaged organs/tissues and via local applications for treatment of local external surgical diseases such as burns, ulcers, and wounds (3,6,18,23).…”