Acceleration of diabetic wound healing with adipose-derived stem cells, endothelial-differentiated stem cells, and topical conditioned medium therapy in a swine model

Irons, Robin F.; Cahill, Kevin W.; Rattigan, Deviney; Marcotte, Joseph H.; Fromer, Marc W.; Chang, Shaohua; Zhang, Ping; Behling, Eric; Behling, Kathryn C.; Caputo, Francis J.

doi:10.1016/j.jvs.2018.01.065

Cited by 54 publications

(41 citation statements)

References 25 publications

(27 reference statements)

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“…It should also be noted that our unique outcomes reveal the synergistic impact of PBM+ADS on skin injury repair in comparison with other related experiments that only investigated the impression of a solo cure with either PBM44 or ADS 18…”

Section: Discussionmentioning

confidence: 63%

“…Probes using animal simulation18 and studies in humans19 have been performed to display the probable favorable impacts of ADS in wounds and ischemic organs in animals and in patients who suffer from DM. Despite the current achievements, several chief obstacles remain before they can be effectively used to benefit diabetic ADS in wound repair.…”

Section: Introductionmentioning

confidence: 99%

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Combined therapy of photobiomodulation and adipose-derived stem cells synergistically improve healing in an ischemic, infected and delayed healing wound model in rats with type 1 diabetes mellitus

Ebrahimpour-Malekshah

Amini

Zare

et al. 2020

BMJ Open Diab Res Care

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ObjectiveWe assessed the therapeutic effects of photobiomodulation (PBM) and adipose-derived stem cell (ADS) treatments individually and together on the maturation step of repairing of a delayed healing wound model in rats with type 1 diabetes mellitus (DM1).Research design and methodsWe randomly assigned 24 rats with DM1 to four groups (n=6 per group). Group 1 was the control (placebo) group. In group 2, allograft human ADSs were transplanted. Group 3 was subjected to PBM (wavelength: 890 nm, peak power output: 80 W, pulse frequency: 80 Hz, pulsed duration: 180 ns, duration of exposure for each point: 200 s, power density: 0.001 W/cm2, energy density: 0.2 J/cm2) immediately after surgery, which continued for 6 days per week for 16 days. Group 4 received both the human ADS and PBM. In addition, we inflicted an ischemic, delayed healing, and infected wound simulation in all of the rats. The wounds were infected with methicillin-resistant Staphylococcus aureus (MRSA).ResultsAll three treatment regimens significantly decreased the amount of microbial flora, significantly increased wound strength and significantly modulated inflammatory response and significantly increased angiogenesis on day 16. Microbiological analysis showed that PBM+ADS was significantly better than PBM and ADS alone. In terms of wound closure rate and angiogenesis, PBM+ADS was significantly better than the PBM, ADS and control groups.ConclusionsCombination therapy of PBM+ADS is more effective that either PBM or ADS in stimulating skin injury repair, and modulating inflammatory response in an MRSA-infected wound model of rats with DM1.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Combined therapy of photobiomodulation and adipose-derived stem cells synergistically improve healing in an ischemic, infected and delayed healing wound model in rats with type 1 diabetes mellitus

Ebrahimpour-Malekshah

Amini

Zare

et al. 2020

BMJ Open Diab Res Care

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“…With regard to large animal models, particularly pigs, ASCs and their potential to improve cutaneous wound healing have been investigated in several studies [23,[100][101][102][103][104] [ Table 2]. James et al] [101] performed a dose-response study of allogenic porcine ASCs delivered into four-centimeter circular full-thickness excisional wounds.…”

Section: Wound Healing In Skinmentioning

confidence: 99%

Adipose-Derived Stromal/Stem Cells from Large Animal Models: from Basic to Applied Science

Bukowska

Szóstek‐Mioduchowska

Kopcewicz

et al. 2020

Stem Cell Rev and Rep

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Adipose-derived stem cells (ASCs) isolated from domestic animals fulfill the qualitative criteria of mesenchymal stem cells, including the capacity to differentiate along multiple lineage pathways and to self-renew, as well as immunomodulatory capacities. Recent findings on human diseases derived from studying large animal models, have provided evidence that administration of autologous or allogenic ASCs can improve the process of healing. In a narrow group of large animals used in bioresearch studies, pigs and horses have been shown to be the best suited models for study of the wound healing process, cardiovascular and musculoskeletal disorders. To this end, current literature demonstrates that ASC-based therapies bring considerable benefits to animal health in both spontaneously occurring and experimentally induced clinical cases. The purpose of this review is to provide an overview of the diversity, isolation, and characterization of ASCs from livestock. Particular attention has been paid to the functional characteristics of the cells that facilitate their therapeutic application in large animal models of human disease. In this regard, we describe outcomes of ASCs utilization in translational research with pig and horse models of disease. Furthermore, we evaluate the current status of ASC-based therapy in veterinary practice, particularly in the rapidly developing field of equine regenerative medicine. In conclusion, this review presents arguments that support the relevance of animal ASCs in the field of regenerative medicine and it provides insights into the future perspectives of ASC utilization in animal husbandry. Graphical abstract

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“…Using a rat model of an ischemic wound (Fisher 344 rats, full-thickness excisional wounds created with a 6 mm punch biopsy), Cooper et al [61] reported that ASC-CM collected from ASCs cultured for 48 h in serum-free MSC basal medium and applied at 20 µL to each wound daily significantly accelerated ischemic wound closure compared to unconditioned medium. Irons et al [68] recently showed that after topical application of CM collected from ASCs isolated from the gluteal region of Yorkshire pigs, the diabetic wound healing in the same animals was significantly enhanced, with concomitant increased angiogenesis and immunomodulation. ASCs were cultured with M-199 medium with 10% FBS and then harvested at 90% confluence, and the cell pellets were resuspended with phosphate buffered solution (PBS).…”

Section: In Vivo Experimental Studiesmentioning

confidence: 99%

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

Lombardi

Palumbo

Augello

et al. 2019

IJMS

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Wound healing is a complex process with a linear development that involves many actors in a multistep timeline commonly divided into four stages: Hemostasis, inflammation, proliferation, and remodeling. Chronic non-healing wounds fail to progress beyond the inflammatory phase, thus precluding the next steps and, ultimately, wound repair. Many intrinsic or extrinsic factors may contribute to such an occurrence, including patient health conditions, age-related diseases, metabolic deficiencies, advanced age, mechanical pressure, and infections. Great interest is being focused on the adipose tissue-derived stem cell’s (ASC) paracrine activity for its potential therapeutic impact on chronic non-healing wounds. In this review, we summarize the results of in vitro and in vivo experimental studies on the pro-wound healing effects of ASC-secretome and/or extracellular vesicles (EVs). To define an overall picture of the available literature data, experimental conditions and applied methodologies are described as well as the in vitro and in vivo models chosen in the reported studies. Even if a comparative analysis of the results obtained by the different groups is challenging due to the large variability of experimental conditions, the available findings are undoubtedly encouraging and fully support the use of cell-free therapies for the treatment of chronic non-healing wounds.

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Acceleration of diabetic wound healing with adipose-derived stem cells, endothelial-differentiated stem cells, and topical conditioned medium therapy in a swine model

Abstract: Cellular therapy with ASCs, EC/ASCs, and topical CM accelerated diabetic wound healing in the swine model. Enhanced angiogenesis and immunomodulation might be key contributors to this process.

Cited by 54 publications

References 25 publications

Combined therapy of photobiomodulation and adipose-derived stem cells synergistically improve healing in an ischemic, infected and delayed healing wound model in rats with type 1 diabetes mellitus

Combined therapy of photobiomodulation and adipose-derived stem cells synergistically improve healing in an ischemic, infected and delayed healing wound model in rats with type 1 diabetes mellitus

Adipose-Derived Stromal/Stem Cells from Large Animal Models: from Basic to Applied Science

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

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