Human mesenchymal stem cells conditioned media promotes the wound healing process - An in vitro study

Jain, Rashi K; Vakil, Devashree; Cunningham, Corey N.; Sidhu, Kuldip

doi:10.29328/journal.jsctt.1001016

Cited by 3 publications

(4 citation statements)

References 15 publications

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“…For instance, conditioned media (CM) promoted proliferation and migration of alveolar epithelial cells facilitating in vitro wound closure. [18][19][20][21] SFCM displayed beneficial effects in a Balb/C mouse model of excisional wound injury via increased deposition of regulatory macrophages and endothelial progenitor cells at the site of injury. 22 Additionally, there was improved functional recovery following hindlimb injury, induced by femoral artery ligation, via increased collateral angiogenesis and limb remodelling.…”

Section: Introductionmentioning

confidence: 98%

Physoxia alters human mesenchymal stem cell secretome

2021

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The human mesenchymal stem cell (hMSC) secretome has pleiotropic effects which underpin their therapeutic potential. hMSC serum-free conditioned media (SFCM) has been determined to contain a variety of cytokines with roles in regeneration and suppression of inflammation. Physiological oxygen (physoxia) has been demonstrated to impact upon a number of facets of hMSC biology and we hypothesized that the secretome would be similarly modified. We tested a range of oxygen conditions; 21% O2 (air oxygen (AO)), 2% O2 (intermittent hypoxia (IH)) and 2% O2 Workstation (physoxia (P)) to evaluate their effect on hMSC secretome profiles. Total protein content of secretome was upregulated in IH and P (>3 fold vs AO) and IH (>1 fold vs P). Focused cytokine profiling indicated global upregulation in IH of all 31 biomolecules tested in comparison to AO and P with basic-nerve growth factor (bNGF) and granulocyte colony-stimulating factor (GCSF) (>3 fold vs AO) and bNGF and Rantes (>3 fold vs P) of note. Similarly, upregulation of interferon gamma-induced protein 10 (IP10) was noted in P (>3 fold vs AO). Interleukin-2 (IL2) and Rantes (in AO and P) and adiponectin, IL17a, and epidermal growth factor (EGF) (in AO only) were entirely absent or below detection limits. Quantitative analysis validated the pattern of IH-induced upregulation in vascular endothelial growth factor (VEGF), placental growth factor-1 (PIGF1), Tumor necrosis factor alpha (TNFa), IL2, IL4, and IL10 when compared to AO and P. In summary, modulation of environmental oxygen alters both secretome concentration and composition. This consideration will likely impact on delivering improved mechanistic understanding and potency effects of hMSC-based therapeutics.

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Section: Introductionmentioning

confidence: 98%

Physoxia alters human mesenchymal stem cell secretome

2021

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“…Exosome potency assays include inhibiting T cell proliferation, macrophage phagocytosis, fibroblast activity, vascular-like network formation assay on Matrigel [167] and scratch wound healing assays [168] that are very useful and can be optimized quickly in the lab. Emerging in vivo potency assays such as EV-mediated wound healing [166,169] (assess the biological response of exosomes in a disease model [170]. Critically understanding the mechanism of how exosomes elicit a response will assist in regulatory approval.…”

Section: Technical Challengesmentioning

confidence: 99%

Stem Cell-Derived Exosomes as New Horizon for Cell-Free Therapeutic Development: Current Status and Prospects

Vakil¹,

Doshi²,

Mckinnirey³

et al. 2023

Possibilities and Limitations in Current Translational Stem Cell Research

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Exosomes have come a long way since they were first described in 1981 by Trams et al. as small lipid bilayer-enclosed vesicles of endocytic origin. Their ability to alter cell bioactivity combined with their advancing popularity as disease biomarkers and therapeutic delivery systems has compelled major Government institutions and regulatory authorities to invest further in this ever-growing field of research. Being relatively new, exosome research is besieged by challenges including but not limited to inefficient separation methods and preservation techniques, difficulties in characterization, and lack of standardized protocols. However, as excitement and research on exosomes increase, their relevance and capacity to elicit a distinct biological response is reinforced. Therefore, it is pertinent to further explore their potential as cell-free therapeutics. This review focuses on current difficulties and subsequent strategies to refine existing methodologies for efficient clinical translation of exosomes in a streamlined and cost-effective manner. The chapter is briefly divided into subsections, each relevant for sequential therapeutic development such as their classification, isolation, scaling up, storage, characterizations, regulatory requirements, therapeutic developments, and perspectives. Apart from literature search, we have endeavored to bring in our own experience in this field including some recent clinical developments.

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“…that are responsible for cell proliferation, fibroblast migration, and angiogenesis essential for wound healing. 14,15 Commonly used methods for delivery of MSC-secretome are systemic and topical administration via injections but challenges with these techniques involve rapid clearance into the circulatory system, short half-life, degradation by macrophages or local tissue environment, and cost of repeated injections are relatively high due to high cost of production and purification. 16 Antunes et al demonstrated that multiple small doses of small EVs had higher wound healing as compared with single high dose of EVs as wound healing is complex multiple day process, which can be achieved using hydrogels by tuning its physical and chemical properties.…”

Section: Introductionmentioning

confidence: 99%

“…Jain et al using our proprietary technology has demonstrated the biocompatibility of MSC‐secretome as well as presence of 105 cytokines and growth factors in the MSC‐secretome like VEGF, FGF, collagen, etc. that are responsible for cell proliferation, fibroblast migration, and angiogenesis essential for wound healing 14,15 16 .…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell‐secretome laden photopolymerizable hydrogels for wound healing

Doshi,

Vakil,

Molley

et al. 2024

J Biomedical Materials Res

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Mesenchymal stem cell‐derived secretome represents an emerging acellular therapeutic which possess significant opportunity for clinical applications due to its anti‐inflammatory, immunomodulatory, and wound healing properties. However, maintaining therapeutic efficacy and ensuring stability of cell‐based products is challenging, requiring a robust delivery method. Therefore, we designed a hydrogel‐based scaffold loaded with CK Cell Technologies' proprietary Mesenchymal stem cell‐secretome for controlled release treatment of acute and chronic wounds. We incorporated both conditioned media (CM) and extracellular vesicles (EVs) into gelatin methacryloyl (GelMA) hydrogels and demonstrated how we can tune the diffusive release of the EVs from them. To demonstrate viability of the approach, we developed a wound healing scratch assay where we see in situ release of CM and EVs promote enhanced migration of human dermal fibroblasts (hDFs). We see the colocalization of these EVs in the fibroblasts using fluorescent microscopy. Finally, as a surrogate for in vivo neovascularization, we conducted an in vitro tube formation assay for the MSC‐secretome using matrigel‐embedded human microvascular endothelial cells. By adding CM and EVs, we observe an increase in tubulogenesis. Collectively, our data demonstrates by tuning the GelMA properties, we can influence the controlled release of the MSC‐secretome for a wound dressing and bandage application for chronic and acute wounds.

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Human mesenchymal stem cells conditioned media promotes the wound healing process - An in vitro study

Abstract: stem cells conditioned media promotes the wound healing process-An in vitro study.

Cited by 3 publications

References 15 publications

Physoxia alters human mesenchymal stem cell secretome

Physoxia alters human mesenchymal stem cell secretome

Stem Cell-Derived Exosomes as New Horizon for Cell-Free Therapeutic Development: Current Status and Prospects

Mesenchymal stem cell‐secretome laden photopolymerizable hydrogels for wound healing

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