Adipose-derived stem cell secretome as a cell-free product for cutaneous wound healing

Ajit, Amita; Gopalankutty, Indu Ambika

doi:10.1007/s13205-021-02958-7

Cited by 18 publications

(18 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human adipose tissue-derived stem cells (hASCs) are a promising therapeutic strategy in regenerative medicine explored in various models of tissue repair, ischemic injuries, immune disorders [ 1 , 2 ], also to improve chronic non-healing or recurrent cutaneous wounds, such as age-associated delayed healing, chronic diabetic wounds, and irradiated wounds [ 3 , 4 ]. Many preclinical and clinical studies have demonstrated that the hASCs secretome enhances wound healing and vascularization mainly by stimulating cell survival, angiogenesis, cell proliferation, ECM cell migration/adhesion, and reducing inflammation [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair

et al. 2022

View full text Add to dashboard Cite

Human adipose tissue-derived stem cells (hASC) secretome display various therapeutically relevant effects in regenerative medicine, such as induction of angiogenesis and tissue repair. The benefits of hASC secretome are primarily orchestrated by trophic factors that mediate autocrine and paracrine effects in host cells. However, the composition and the innate characteristics of hASC secretome can be highly variable depending on the culture conditions. Here, we evaluated the combined effect of serum-free media and hypoxia preconditioning on the hASCs secretome composition and biological effects on angiogenesis and wound healing. The hASCs were cultured in serum-free media under normoxic (NCM) or hypoxic (HCM) preconditioning. The proteomic profile showed that pro- and anti-antiangiogenic factors were detected in NCM and HCM secretomes. In vitro studies demonstrated that hASCs secretomes enhanced endothelial proliferation, survival, migration, in vitro tube formation, and in vivo Matrigel plug angiogenesis. In a full-thickness skin-wound mouse model, injection of either NCM or HCM significantly accelerated the wound healing. Finally, hASC secretomes were potent in increasing endothelial density and vascular coverage of resident pericytes expressing NG2 and nestin to the lesion site, potentially contributing to blood vessel maturation. Overall, our data suggest that serum-free media or hypoxic preconditioning enhances the vascular regenerative effects of hASC secretome in a preclinical wound healing model.

show abstract

Section: Introductionmentioning

confidence: 99%

Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Moreover, it has been shown that ADSC-derived secretome, which includes extracellular vesicles and soluble factors, such as cytokines and growth factors, have a notable impact on improving the healing process of cutaneous wounds [ 9 , 10 , 11 ]. Thus, keeping in mind the advantages of cell-free preparations over cellular products (such as avoiding the use of viable cells and diminishing the variability), developing a ready-to-use medicine based on ADSC-derived secretome for wound healing applications seems promising [ 12 ]. However, the development of such treatment requires the in vitro expansion of cells for a long period of time, which has the disadvantage that the biological material is quickly depleted and additional isolation of primary ADSC is needed, which could negatively impact the variability of the cell products.…”

Section: Introductionmentioning

confidence: 99%

Generation of an Immortalized Human Adipose-Derived Mesenchymal Stromal Cell Line Suitable for Wound Healing Therapy

Iacomi¹,

Rosca²,

Ţuţuianu³

et al. 2022

IJMS

View full text Add to dashboard Cite

Adipose-derived mesenchymal stromal cells (ADSC) are a promising source for cellular therapy of chronic wounds. However, the limited life span during in vitro expansion impedes their extensive use in clinical applications and basic research. We hypothesize that by introduction of an ectopic expression of telomerase into ADSC, the cells’ lifespans could be significantly extended. To test this hypothesis, we aimed at engineering an immortalized human ADSC line using a lentiviral transduction with human telomerase (hTERT). ADSC were transduced with a third-generation lentiviral system and a hTERT codifying plasmid (pLV-hTERT-IRES-hygro). A population characterized by increased hTERT expression, extensive proliferative potential and remarkable (potent) multilineage differentiation capacity was selected. The properties for wound healing of this immortalized ADSC line were assessed after 17 passages. Their secretome induced the proliferation and migration of keratinocytes, dermal fibroblasts, and endothelial cells similarly to untransduced ADSC. Moreover, they sustained the complete re-epithelialization of a full thickness wound performed on a skin organotypic model. In summary, the engineered immortalized ADSC maintain the beneficial properties of parent cells and could represent a valuable and suitable tool for wound healing in particular, and for skin regenerative therapy in general.

show abstract

“…The ASC-patch studied here essentially relies on the combined interaction of adipose-derived stem cells with gelatin. ASCs are known for their ability to enhance the healing process by secretion of soluble healing factors and extracellular vesicles [37][38][39][40]. Here we demonstrate that ASCs not only increase their regenerative potential when they grow within the patch, but are also locally concentrated.…”

Section: Discussionmentioning

confidence: 54%

Efficacy and safety of a patch containing adipose-derived stem cells for skin wound healing – results form a comprehensive pre-clinical evaluation program

Brembilla

Lévigne

et al. 2022

Preprint

View full text Add to dashboard Cite

Mesenchymal stem cell-based therapies are emerging as innovative approaches to treat chronic wounds. A common administration route used in clinical trials consists of local injections leading to uncontrolled/sub-optimal delivery. This study reports a comprehensive pre-clinical evaluation program on the mechanism of action, efficacy and safety of an easy-to-use patch that concentrates Adipose-derived Stem Cells (ASCs) in a clinical-grade sponge of porcine crosslinked-gelatin. ASCs were prepared from the fat of ischemic patients. Transcriptome and proteome of ASC-patches and ASC monolayers were assessed by microarrays, bio-arrays and mass spectrometry. Tumorigenesis was investigated in immunosuppressed mice according to the European Pharmacopeia. Angiogenesis was assessed in vivo in the chick chorioallantoic membrane model. Efficacy of the ASC-patch was tested in a rat model of ischemic full-thickness skin defect. Cell stability was assessed by luminescence using ASC-patches generated from ASCs stably transduced with firefly luciferase. ASCs from ischemic patients upregulated the transcription of multiple genes involved in skin wound healing when cultured within the ASC-patch formulation. The patch was not only a concentrator, but also a reservoir of both ASC-derived regenerative factors and sponge-derived soluble fragments having healing capacity. The secretome of the ASC-patch promoted dermal fibroblast survival and epidermal epithelialization. No tumor formation was observed in immunodeficient Nude mice subcutaneously transplanted with the ASC-patch. Transplanted patches were early invaded by new vessels in vivo, and a marked angiogenesis was confirmed in two independent animal models. Finally, ASC-patches prepared from syngeneic rats promoted faster healing and re-vascularization of full-thickness skin defects in a rat animal model. Of note, ASCs were viable and locally stable for at least two weeks in vivo. We provide here compelling pre-clinical evidence that patches concentrating ASCs within crosslinked gelatin may represent a convenient and effective tool for the management of chronic wounds.

show abstract

Adipose-derived stem cell secretome as a cell-free product for cutaneous wound healing

Cited by 18 publications

References 93 publications

Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair

Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair

Generation of an Immortalized Human Adipose-Derived Mesenchymal Stromal Cell Line Suitable for Wound Healing Therapy

Efficacy and safety of a patch containing adipose-derived stem cells for skin wound healing – results form a comprehensive pre-clinical evaluation program

Contact Info

Product

Resources

About