Erectile dysfunction also synonymously known as ED affects nearly half of men between the ages of 40 and 70 to some extent. Vascular diseases interrelated with aging, hyperlipidemia, smoking, diabetes as well as hypertension, are often linked to erectile dysfunction. Furthermore, injury to cavernous nerves in the penile region “comprises an appreciable number of ED cases.” ⁶ Other causes of erectile dysfunction include but are not limited to endocrine disorders, as well as fibrosis of the penile tissue and corporal smooth muscle.¹¹ Overall both vasculogenic and neurogenic erectile dysfunctions are linked to the loss of normal cellular function or cell death (apoptosis).

Oral medications such as phosphodiesterase-5 inhibitors (PDE5is), have clear benefits, and are typically first-line treatments in regards to erectile dysfunction, however their actions are short lived.⁶ Lifestyle changes and injections are also typical first line treatment options for the management of complex cases of erectile dysfunction. Most recently scientists and physicians have been focusing on new next generation novel therapy options as a way to restore natural sexual function; one such treatment option includes Stem Cell based Bioactive Factor Therapy.

Stem-cell-based therapies focus on the management of erectile dysfunction “through the protection of the threatened host cells via immunomodulatory effects, and the provision of trophic factors or gene delivery.”¹¹ In recent years, a number of research studies related to the progress of stem cell-based erectile dysfunction therapy have been published. This is yielding strong evidence supporting the concept that stem-cell-based bio-active therapy is potentially the next generation therapeutic approach for erectile dysfunction. Furthermore, research studies conducted have taken into account a large spectrum of stem cells, including mesenchymal stem cells, tissue as well as muscle -derived stem cells for further investigation in regards to vascular, neural, endothelial or smooth muscle regeneration in animal models for erectile dysfunction.

What are Mesenchymal Stem Cells?

Stem cells are cells that differentiate into smooth muscle cells, neurons, endothelial cells and other types of varying cells. Stem cells by definition have the capability of self-renewal, meaning that they can make copies of themselves for an indefinite period, and differentiate into a variety of phenotypes.^{1, 2} Stem cells are defined by their “capacity for both self-renewal and directed differentiation. Thus, they represent great promise for regenerative medicine.” Stem cells can be categorized as either embryonic stem cells (ESCs) or adult stem cells (ASCs). Embryonic stem cells (ESCs) are acknowledged as an example of pluripotent cells.⁶ While multipotent stem cells include mesenchymal stem cells (MSCs) as they “are capable of self-renewal, and they can differentiate into any cell type within their germ layer”.⁴

Stem cells have diverse properties that make them potentially viable for utilization in various disease treatments. In particular, adult MSCs are “multipotent cells that undergo self-renewal and differentiation” as well as express specific surface markers.¹³ MSCs can be derived from different sources within the body, including adipose tissue, bone marrow as well as the umbilical cord membrane. ^{13, 12} Historically, MSCs were founded by a researcher named Friedenstein through the conduction of studies on the bone marrow although MSCs can be isolated from other adult tissues including adipose tissue. ^{7, 5} The word “Stem Cells” more correctly known as “Mesenchymal Stem Cells” (MSCs) were termed MSCs secondary to their innate ability to duplicate while maintaining the attribute of multi-potential lineage.

MSCs “contain growth factors, signaling lipids, mRNAs, and regulatory miRNAs, which are involved in tissue repair as paracrine mediators.” ^{13, 14} Research studies have also suggested that exosomes released by MSCs may aid erectile dysfunction linked to diabetes through anti-fibrotic mechanisms, preventing cell death as well as increasing smooth and endothelial muscle content. ^{15, 18}

What are Bioactive Factors and EVs?

MSCs are able to secrete soluble “Bioactive Factors” which aid in modulating the immune system, improve the standard rate of healing injured tissues and reduce inflammation. Stem Cell Bioactive Factors consist of nanoparticles which are released from the membranes of Mesenchymal Stem Cells (MSCs). These nanoparticles contain over “200 Growth factors, Cytokines and Nucleic Acids which support healthy cell-to-cell communication and are responsible for the therapeutic effects observed in regenerative medicine.”

EVs or extracellular vesicles are membrane-packed vesicles that are secreted by MSCs. ⁹ EVs have been demonstrated to perform a critical role in cell-to-cell communication and important processes such as immune responses, homeostasis maintenance, and more. ^{8, 9}

Microvesicles, an important EV, may “change functional target cells by delivering intracellular proteins”; for example, MVs released from endothelial cells can promote the regeneration through transfer of growth factors and their activators. ¹² MSC-derived EVs (MSC-EVs) based stem cell therapies are easier to manage and safer “due to their inability to directly form tumors.” ¹⁰

Mesenchymal Stem Cell’s Bioactive Factors

Bioactive Factors demonstrate numerous advantages when compared to Mesenchymal Stem Cells: