Genetic engineering of mesenchymal stem cells by non-viral gene delivery

Abstract

Mesenchymal stem cells (MSCs) are an ideal cell source for tissue engineering and regenerative medicine as they possess self-renewal properties and multilineage differentiation potential. They can be isolated from various tissues and expanded easily through normal cell culture techniques. Genetic modifications of MSCs to further improve their therapeutic efficacy have been widely studied and extensively researched. Compared to viral gene delivery methods, non-viral methods generate less toxicity and immunogenicity and thus represent a promising and effective tool for the genetic engineering of MSCs. In the last decades, various non-viral gene delivery strategies have been developed and some of them have been applied for MSC transfection. This paper gives an overview of the techniques, influencing factors and potential applications of non-viral methods used for the genetic engineering of MSCs.

A Dermal Equivalent Engineered with TGF‐β3 Expressing Bone Marrow Stromal Cells and Amniotic Membrane: Cosmetic Healing of Full‐Thickness Skin Wounds in Rats

“…The safety of plasmid gene delivery method used in the current study is higher than the viral methods in terms of immunogenicity and insertional mutagenesis (see Wang et al, 2014 for review [44]). The transient nature of transfection and increased expression of TGF-b3 only during days 3-7 posttransfection provides an additional index of safety.…”

Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

“…Cumulating evidence have shown hopeful results of this method in the treatment of neurodegenerative, inflammatory and autoimmune diseases (126). Genetic modification of MSCs can drive different processes of cell differentiation like osteogenesis, adipogenesis, angiogenesis, and chondrogenesis (127). MSCs secrete several proangiogenic factors which promote formation of new vessels when used without any modifications (127).…”

“…Genetic modification of MSCs can drive different processes of cell differentiation like osteogenesis, adipogenesis, angiogenesis, and chondrogenesis (127). MSCs secrete several proangiogenic factors which promote formation of new vessels when used without any modifications (127). One of the most important proangiogenic factors is VEGF (128).…”

“…Overexpression of adrenomedullin which produces a peptide promoting angiogenesis in MSCs improved capillary density and cardiac function in infarcted rat heart (130). Bone morphogenetic proteins (BMPs) and TGF-β are two important factors that are used generally to promote osteogenesis and chondrogenesis (127).…”

“…On the other hand, non-viral methods show low transfection efficiency and transgene expression for a shorter period of time. However, they are less toxic and safer and also larger size of genes can be transferred into MSCs by using these methods (127).…”