Genetic Stability of Mesenchymal Stromal Cells for Regenerative Medicine Applications: A Fundamental Biosafety Aspect

Abstract

Mesenchymal stem/stromal cells (MSC) show widespread application for a variety of clinical conditions; therefore, their use necessitates continuous monitoring of their safety. The risk assessment of mesenchymal stem cell-based therapies cannot be separated from an accurate and deep knowledge of their biological properties and in vitro and in vivo behavior. One of the most relevant safety issues is represented by the genetic stability of MSCs, that can be altered during in vitro manipulation, frequently required before clinical application. MSC genetic stability has the potential to influence the transformation and the therapeutic effect of these cells. At present, karyotype evaluation represents the definitely prevailing assessment of MSC stability, but DNA alterations of smaller size should not be underestimated. This review will focus on current scientific knowledge about the genetic stability of mesenchymal stem cells. The techniques used and possible improvements together with regulatory aspects will also be discussed.

An Update on the Progress of Isolation, Culture, Storage, and Clinical Application of Human Bone Marrow Mesenchymal Stem/Stromal Cells

“…The International Society for Cellular Therapy (ISCT) defines the minimal criteria of mesenchymal stem cells [8]. MSCs have been demonstrated to differentiate into different cell lineages which regulate the immune system and induce anti-inflammation [9]. During treatment, the infused MSCs can bring effects on injured or inflammation sites.…”

“…The number of stem cells is limited in bone marrow (0.42%) when compared to adipose tissue and umbilical cord, thus the expansion and cultivation of BMSCs are required to obtain an efficient number of cells for treatment [16]. However, the expansion process highly contributes to genetic instability, senescence, and transformation issues [9]. In general, in-vitro expansion cells reduce the genetic stability of native BMSCs [9,17].…”

“…However, the expansion process highly contributes to genetic instability, senescence, and transformation issues [9]. In general, in-vitro expansion cells reduce the genetic stability of native BMSCs [9,17]. In vitro expansion reduces DNA polymerase and repair capacity, thus resulting in DNA damage accumulation [9].…”

Characterization of Mesenchymal Stem Cells Derived from Patients with Cerebellar Ataxia: Downregulation of the Anti-Inflammatory Secretome Profile

“…MSCs from type 2 diabetes patients showed upregulated autophagy and mitochondria deterioration that indirectly affect MSC fate [42]. Although underestimated, epigenetic and genetic instability might also affect longevity and regenerative capacity of MSCs [43]. In this study, the secretome analyses revealed the reduced cell proliferation, migration, and anti-inflammatory capacity (TGF-β signaling pathway) in CA-MSCs (Supplemental Figure S2).…”

Secretome of Adipose Tissue-Derived Stem Cells (ASCs) as a Novel Trend in Chronic Non-Healing Wounds: An Overview of Experimental In Vitro and In Vivo Studies and Methodological Variables

“…However, there are still unresolved critical issues for the definition of effective ASC therapy, which include, among others, the need to standardize methods of isolation, culture, expansion, and characterization of ASCs as well as appropriate quality and safety control for cell-based therapies [31][32][33][34]. Each step of preparation, purification, and expansion of ASCs can, in fact, compromise the quality of the ASCs, leading to progressive cellular senescence, genomic instability, reduction of the level of proliferation, and gradual loss of differentiative potential [35,36]. Other factors that can strongly affect the safety, quality, and properties of ASCs include either the anatomical site of adipose tissue removal/lipoaspirate or the general conditions of the donor (age, body mass index, age-related chronic diseases) [22].…”