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Review
. 2021 Mar 19:9:654885.
doi: 10.3389/fcell.2021.654885. eCollection 2021.

Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy

Rebecca M Harman  1 , Charlotte Marx  1 , Gerlinde R Van de Walle  1
Affiliations
Review

Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy

Rebecca M Harman et al. Front Cell Dev Biol. .

Abstract

The therapeutic potential of the mesenchymal stromal cell (MSC) secretome, consisting of all molecules secreted by MSCs, is intensively studied. MSCs can be readily isolated, expanded, and manipulated in culture, and few people argue with the ethics of their collection. Despite promising pre-clinical studies, most MSC secretome-based therapies have not been implemented in human medicine, in part because the complexity of bioactive factors secreted by MSCs is not completely understood. In addition, the MSC secretome is variable, influenced by individual donor, tissue source of origin, culture conditions, and passage. An increased understanding of the factors that make up the secretome and the ability to manipulate MSCs to consistently secrete factors of biologic importance will improve MSC therapy. To aid in this goal, we can draw from the wealth of information available on secreted factors from MSC isolated from veterinary species. These translational animal models will inspire efforts to move human MSC secretome therapy from bench to bedside.

Keywords: human; mesenchymal stromal cells; secretome; stem cells; translational models; veterinary.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Bioactive components of the mesenchymal stromal cell (MSC) secretome. The MSC secretome is comprised of all factors secreted by MSCs. The bioactive components of the secretome include a wide range of small molecules, nucleic acids (importantly, regulatory RNAs), peptides, and proteins. These molecules can either be released freely or packaged in extracellular vesicles, which are lipid bilayer-delimited particles of various size and composition.
FIGURE 2
FIGURE 2
Altering the mesenchymal stromal cell (MSC) secretome through in vitro manipulation. In order to increase the secretion of desired molecules, such as proteins or miRNA, MSCs are manipulated in culture through either priming or genetic engineering. The four main approaches of priming are (i) addition of pharmacological/chemical agents, (ii) treatment with cytokines, (iii) culture in 3D cultures/bio-scaffolds, and (iv) culture under induced hypoxic conditions. Genetic engineering is used to express/overexpress specific proteins or miRNA by a targeted RNA or DNA transfer into the MSCs via transduction, transfer by virus or viral vector, or transfection, transfer through various biological/chemical/physical approaches. DMOG, dimethyloxalylglycine; LPS, lipopolysaccharides; PPS, pentosan polysulfate; IL, interleukin; IFN, interferon; TNF, tumor necrosis factor; 3D, 3-dimensional; O2, oxygen.
FIGURE 3
FIGURE 3
Diseases in veterinary species as translational models for human disease. Small companion animals (i.e., dogs and cats), as well as large animals (i.e., pigs and horses), develop pathologies that are similar to diseases in humans and thus, are used as translational animal models for neurological, cardiac, pulmonary, musculoskeletal, nephrological, gastroenterological, dermatological, infectious, and cancerous, diseases. Body sizes are not to scale. IBD, inflammatory bowel disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease.
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