Stem cell secretome, regeneration, and clinical translation: a narrative review

Abstract

Regenerative medicine is a field growing in popularity due to high hopes for stimulating in situ tissue restoration. Stem cell therapy remain at the center of regenerative medicine, due to early reports on its pluripotent differentiating capability. However, more recent reports suggest the paracrine activity of stem cells, and not direct differentiation, as the cause of its therapeutic effects. This paracrine activity can be harnessed in the form of conditioned media. Despite these capabilities, the clinical translation of stem cell conditioned media (i.e., secretome) is precluded by a variety of factors. These limitations include standardization of stem cell-conditioned media formulation, characterization of bioactive factors in conditioned media and dosing, optimizing modes of delivery, and uncovering of mechanisms of action of stem cell conditioned media. The purpose of this review is to provide a focused narration on the aforementioned preclusions pertaining to the clinical translation of stem cell conditioned media. Specifically, we will report on commonly use methodologies for the development of stem cell conditioned media, modalities for conditioned media characterization, modes of delivery, and postulated mechanisms of action for stem cell conditioned media in regenerative medicine.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury

“…MSCs are the most widely used cells for AKI treatment and allograft protocols because they can be obtained from bone marrow and expanded in culture ( 17 ). MSCs originate from the mesoderm and have the ability to differentiate into mesenchymal and non-mesenchymal cell lines, including bone and cartilage ( 17 ).…”

“…For example, compared with cord blood-derived MSCs, signals mediated by EVs derived from bone marrow MSCs had greater effects on bone growth and differentiation ( 49 , 114 ). In addition, adipose-derived MSCs had similar immune regulation effects to bone marrow-derived MSCs ( 17 ). The EV source should be selected flexibly according to the type of kidney injury and treatment needs.…”

“…Among these, mesenchymal stem cells (MSCs) are considered to be one of the most promising types of cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to be stored and expanded in vitro (15,16). Notably, numerous preclinical and clinical studies have confirmed the potential role of MSCs in kidney protection and repair (17)(18)(19)(20)(21)(22). However, the mechanisms by which MSCs exert their therapeutic effects remain controversial.…”

“…Several studies have also demonstrated that MSCs depend on complex and powerful endocrine and paracrine functions, and secrete extracellular vesicles to promote the recovery of renal function in AKI ( 24 , 25 ). Secretion of growth factors, regulation of the inflammatory response, promotion of mitosis and cell proliferation, anti-apoptosis and anti-inflammatory effects, the reduction of fibrosis, and the promotion of angiogenesis have been reported in multiple studies ( 17 ). However, the main therapeutic effects of MSCs appear to be mediated by MSC-EVs, rather than by the MSCs themselves ( 26 ).…”

Application of Multipotent Mesenchymal Stem Cell Secretome in the Treatment of Adjuvant Arthritis and Contact-Allergic Dermatitis in Animal Models

“…Volume VIII, Issue 6, 2020 directions of the MMSC actions can be considered as follows: secretion of biologically active substances, microvesicles, exosomes [5,6]. The secret of MMSCs contains a wide range of biologically active substances, possesses immunomodulatory properties, and therefore is potentially applicable in therapy without any use of the cells themselves [7].…”