Atherosclerosis is the most common form of arterial occlusive disease in adults.  About 15 percent of adults over 55 years of age suffer from critical ischemia, the most severe form of this disease.

Due to the gradual aging of the population and the growing number of people in their third age group, a number of studies have been conducted in order to improve the prognosis of atherosclerosis obliterans and to find alternatives to the mutilation of the extremities. As a general rule, chronic ischemia of the lower limbs should be treated to alleviate symptoms, particularly pain, prevent disease progression, and reduce the rate of amputations. In most patients with critical ischemia, the main goal is to preserve the affected limb.

The development of regenerative medicine is closely linked to the development of new knowledge about embryonic and adult stem cells, as well as the regenerative and therapeutic potential of stem cell therapy. The use of adult stem cells in the treatment of peripheral artery diseases has been demonstrated as a therapeutic agent for inducing angiogenesis. Recent preclinical studies as well as the pioneering clinical studies indicate that bone marrow-derived mononuclear cells (MBMCs) can enhance tissue vascularization in ischemic limbs, with results similar to those obtained with peripheral blood stem cells supply.

Cuba presented the first studies carried out in 2004 at the Institute of Hematology of the “Enrique Cabrera” hospital in Havana City, which achieved encouraging clinical results and had very few adverse effects in recent years.

A progressive rise in the accumulated experience with stem cells was also observed in Pinar del Rio in 2005, as the first 10 cases were carried out. The rising ease of obtaining this type of cell has made research and applications with these cells advance rapidly with great expectations in terms of clinical application.

A study published by Dia-Diaz, et al. in the Journal of Medical Sciences of Pinar del Rio examined 296 patients with grade IV atherosclerosis obliterans between 2009 and 2019. During the study, autologous stem cells were injected intramuscularly from peripheral blood. Within four weeks, pain relief was observed, as well as an increase in the pain-free claudication distance. Angiography after treatment revealed collateral vessel formation. The limb was saved in 201 patients (68%), while 95 cases (32%) presented amputation criteria. Complications were not reported following the procedure.

The study demonstrated the effectiveness of the implantation of autologous stem cells obtained from peripheral blood, as well as the favorable evolution of patients, clinical improvement of rest pain, walking distance without claudication and ankle-brachial pressure index.

We still need to explore a lot of ground, in terms of these and other conditions. You can learn more about regenerative medicine and stem cells by enrolling in our international certification program at www.issca.us

In recent years, MSCs have been introduced as respectable candidates for regenerative medicine due to their pro-angiogenic, anti-apoptotic, and immunomodulatory attributes. A variety of human tissues can be used as a source of mesenchymal stem/stromal cells (MSCs), ranging from bone marrow (BM) to umbilical cord (UC). These cells are typically multipotent and can differentiate into a variety of cell types. MSCs have been studied extensively for potential applications in cardiomyopathy, neurodegenerative disorders, spinal cord injuries (SCI), kidney injuries, liver injuries, lung injuries, and even cancer. According to current research, MSC-derived extracellular vesicles (EVs) contribute to MSC-exerted therapeutic benefits.

As defined by the International Society for Extracellular Vesicles (ISEV), EVs are lipid bilayer particles secreted by cells that do not replicate. EVs can be categorised into three subclasses based on size and biogenesis procedures: surrounding exosomes (50-150 nm), microvesicles (MVs) (100-1000 nm), and apoptotic bodies (ApoBDs) (500-5000 nm). In order for exosomes to be produced, multiple steps must occur; endosomes must be created from the plasma membrane, intraluminal vesicles must be formed within multivesicular bodies by inward budding, the MVB must merge with the plasma membrane, and finally the internal vesicles must be released.

By transmitting their molecules, such as proteins, messenger RNA (mRNA), and microRNAs (miRNAs), MSC exosomes stimulate phenotypic changes and subsequently modify regenerative programs of target organs. A number of mechanisms are involved in phenotypic alterations, including prevention of apoptosis, cell proliferation, immunomodulatory reactions, attenuation of oxidative stress, and improving oxygen supply to recipient cells. By supporting mitochondrial transfer, MSC-exosomes can suppress inflammatory cytokine production and induce phenotype 2 alveolar macrophages (M2), leading to acute lung injury (ALI) rescue. It has been demonstrated that the transmission of miRNAs from MSC-exosomes to recipient cells is responsible for the restoration of damaged kidneys, hearts, livers, and brains

Various cells continuously form and secrete exosomes, including lymphocytes, platelets, mast cells, intestinal epithelium, dendritic cells, neoplastic cell lines, microglia, neurons, and MSCs. Studies have shown that exosomes play an important role in cell-to-cell communication as well as several physiological and pathological processes. Despite their inherent biological activities, exosomes have recently been introduced as encouraging drug carriers because of their small size, high biocompatibility, and ability to hold different therapeutic ingredients, including proteins, nucleic acids, and small molecules. There have been reports showing the usefulness of MSCs-exosomes for treating a variety of ailments, such as lung, kidney, liver, neurodegenerative, cardiac, and musculoskeletal diseases, as well as skin wounds in vivo.

As well as their remarkable therapeutic effects, MSC-EVs derived from diverse sources also possess a variety of physiological functions that may affect their therapeutic application. In a wide range of human disorders, MSC-exosomes are considered an effective alternative to whole-cell therapy because of their low immunogenicity and improved safety profile. Although MSC-exosome applications still face various challenges, their benefits and capabilities are attracting increasing interest.

To learn more about exosomes and their clinical applications or if you’re interested in boosting your clinical practice with exosomes, go to our website www.cellgenic.com