Autologous Bone-Marrow vs. Peripheral Blood Mononuclear Cells Therapy for Peripheral Artery Disease in Diabetic Patients

Abstract

Diabetes mellitus (DM) remains one of the most important risk factors for peripheral artery disease (PAD), with approximately 20% of DM patients older than 40 years old are affected with PAD. The current standard management for severe PAD is endovascular intervention with or without surgical bypass. Unfortunately, up to 40% of patients are unable to undergo these revascularization therapies due to excessive surgical risk or adverse vascular side effects. Stem cell therapy has emerged as a novel therapeutic strategy for these ‘no-option’ patients. Several types of stem cells are utilized for PAD therapy, including bone marrow mononuclear cells (BMMNC) and peripheral blood mononuclear cells (PBMNC). Many studies have reported the safety of BMMNC and PBMNC, as well as its efficacy in reducing ischemic pain, ulcer size, pain-free walking distance, ankle-brachial index (ABI), and transcutaneous oxygen pressure (TcPO2). However, the capacity to establish the efficacy of reducing major amputation rates, amputation free survival, and all-cause mortality is limited, as shown by several randomized placebo-controlled trials. The present literature review will focus on comparing safety and efficacy between BMMNC and PBMNC as cell-based management in diabetic patients with PAD who are not suitable for revascularization therapy.

Target and Cell Therapy for Atherosclerosis and CVD

“…Stem cells are capable of self-renewing and producing differentiated cells. Based on the degree of differentiation, they can be divided into totipotent, pluripotent, multipotent, oligopotent, or unipotent [ 117 ]. Bone marrow stem cells include various types of progenitor cells: multipotent adult progenitor cells, MSCs, and hematopoietic stem cells [ 118 ].…”

New technologies for tissue replacement

“…Since the discovery that blood cells contribute to postnatal angiogenesis (276), there has been an increasing number of clinical studies to test the efficacy of autologous cell therapies for the treatment of CLTI, ranging from case reports to small series, uncontrolled trials and RCTs reported in numerous meta-analyses (277)(278)(279)(280)(281)(282)(283)(284)(285). The main goal of cell therapy is the induction of therapeutic angiogenesis with the formation of collaterals leading to increased blood flow in the ischemic limb and tissue regeneration in non-healing wounds.…”

Stem cells therapy in patients with chronic limb-threating ischemia

“…V průměru u 40 % pacientů s CLTI však není možné provést PTA ani jiný způsob revaskularizace (9). Tyto případy jsou označované jako "no-option CLTI" a jsou prediktorem nehojících se defektů a neúspěchu chirurgických zákroků (3).…”

“…Kromě toho BMMNC i PBMMNC mají schopnost sekrece pro-angiogenních faktorů, jako vaskulární endoteliální růstový faktor (VEGF), fibroblastový růstový faktor (bFGF), růstový faktor hepatocytů (HGF) a angiopoein-1. Tímto parakrinním účinkem dále přispívají k podpoře neovaskularizace (9). U MSC byly popsány tři mechanismy neovaskularizace, a to parakrinní aktivita, ke které se radí i jejich imunomodulační účinek, dále přímá diferenciace a mitochondriální transfer.…”