Development of a combined radiation and full thickness burn injury minipig model to study the effects of uncultured adipose-derived regenerative cell therapy in wound healing

Foubert, Philippe; Doyle-Eisele, Melanie; Gonzalez, Andreina D.; Berard, Felipe; Weber, Waylon; Zafra, Diana; Alfonso, Zeni; Zhao, Sherry; Tenenhaus, Mayer; Fraser, John K.

doi:10.1080/09553002.2017.1242814

Cited by 21 publications

(24 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fourteen studies [ 16 , 28 , 29 , 37 – 39 , 41 , 44 – 50 ] used rats, six studies [ 17 , 30 , 40 , 42 , 43 , 51 ] used mice, and two studies [ 36 , 52 ] used minipigs. A total of 10 studies were conducted in China [ 29 , 30 , 37 , 39 , 40 , 43 , 47 – 49 , 51 ], 3 studies in Brazil [ 16 , 28 , 41 ], 3 studies in the USA [ 36 , 42 , 52 ], and 2 studies in Iran [ 38 , 45 ], whereas the remaining 4 were conducted in Pakistan [ 46 ], Egypt [ 44 ], Turkey [ 50 ], and Canada [ 17 ], respectively. Four studies [ 40 , 43 , 48 , 51 ] did not report burn degree and two [ 38 , 45 ] used second-degree burns, while the others used third-degree.…”

Section: Resultsmentioning

confidence: 99%

“…Four studies [ 40 , 43 , 48 , 51 ] did not report burn degree and two [ 38 , 45 ] used second-degree burns, while the others used third-degree. The cell types used for transplantation were mesenchymal stem cells (MSCs) [ 17 , 28 – 30 , 43 – 48 , 50 ], epidermal stem cells (ESCs) [ 40 , 51 ], hair follicle stem cells (HFSCs) [ 38 ], stromal vascular fraction (SVF) [ 36 , 52 ], and adipose-derived stem cells (ASCs) [ 16 , 37 , 39 , 41 , 42 , 49 ]. As for mesenchymal stem cells, they derived from umbilical cord [ 30 , 46 – 48 ], bone marrow [ 28 , 29 , 43 – 45 , 50 ], and burned tissue [ 17 ].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of stem cell therapy for burn wounds: a systematic review and meta-analysis of preclinical studies

Xia

Merwe

et al. 2020

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Burns remain a serious public health problem with high morbidity and mortality rates worldwide. Although there are various treatment options available, there is no consensus on the best treatment for severe burns as of yet. Stem cell therapy has a bright prospect in many preclinical studies of burn wounds. The systematic review was performed for these preclinical studies to assess the efficacy and possible mechanisms of stem cells in treating burn wounds. Methods Twenty-two studies with 595 animals were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to 13 May 2020. In addition, a manual search of references of studies was performed to obtain potential studies. No language or time restrictions were enforced. RevMan 5.3 was used for all data analysis. Results The overall meta-analysis showed that stem cell therapy significantly improved burn healing rate (SMD 3.06, 95% CI 1.98 to 4.14), irrespective of transplant type, burn area, and treatment method in the control group. Subgroup analyses indicated that hair follicle stem cells seemed to exert more beneficial effects on animals with burn wounds (SMD 7.53, 95% CI 3.11 to 11.95) compared with other stem cells. Furthermore, stem cell therapy seemed to exert more beneficial effects on burn wounds with second-degree (SMD 7.53, 95% CI 3.11 to 11.95) compared with third-degree (SMD 2.65, 95% CI 1.31 to 4.00). Conclusions Meta-analysis showed that stem cell therapy exerts a healing function for burn wounds, mainly through angiogenesis and anti-inflammatory actions. These findings also demonstrate the need for considering variations in future clinical studies using stem cells to treat a burn wound in order to maximize the effectiveness. In general, stem cells can potentially become a novel therapy candidate for burn wounds.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Efficacy of stem cell therapy for burn wounds: a systematic review and meta-analysis of preclinical studies

Xia

Merwe

et al. 2020

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…Following wound injury (within 2 hours), adipose tissue (30–50 g) was excised from the inguinal fat region of the animals (while under general anesthesia) and isolated as previously described using Celase® enzyme [ 20 – 22 ]. ADRC yield and viability was determined using the NucleoCounter® NC‐100™ (ChemoMetec, Lillerød, Denmark), as previously described [ 22 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

“…In this regard, a number of preclinical and clinical studies have reported that SVF, also referred to as adipose-derived rcgenerative Cells or ADRCs, modulates inflammation [ 8 – 11 ], angiogenesis [ 9 , 11 – 13 ], and tissue fibrosis [ 14 – 19 ]. In our previously reported full-thickness burn studies in a Göttingen porcine model, we were able to show that autologous ADRC delivery improved wound angiogenesis and epithelialization [ 20 – 22 ]. While encouraging, our prior work was limited to assessment of short-term wound healing (up to 4 weeks post-injury) and did not address long term sequelae, such as HTS.…”

Section: Introductionmentioning

confidence: 99%

Autologous adipose-derived regenerative cell therapy modulates development of hypertrophic scarring in a red Duroc porcine model

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundEffective prevention and treatment of hypertrophic scars (HTSs), a common consequence of deep-partial thickness injury, remain a significant clinical challenge. Previous studies from our group have shown that autologous adipose-derived regenerative cells (ADRCs) represent a promising approach to improve wound healing and, thereby, impact HTS development. The purpose of this study was to assess the influence of local delivery of ADRCs immediately following deep-partial thickness cutaneous injury on HTS development in the red Duroc (RD) porcine model.MethodsBilateral pairs of deep-partial thickness excisional wounds (2 mm depth; 58 cm2 area) were created using an electric dermatome on RD pigs (n = 12). Autologous ADRCs were isolated from the inguinal fat pad and then sprayed directly onto the wound at a dose of 0.25 × 106 viable cells/cm2. The paired contralateral wound received vehicle control. Wound healing and development of HTS were assessed over 6 months using digital imaging, quantitative measurement of skin hardness and pigmentation, and histology.ResultsData showed that ADRC treatment led to reduced scar hyperpigmentation compared to control (p < 0.05). Using the Durometer, at 2 and 6 months post-injury, skin hardness was 10–20% lower in ADRCs-treated wounds compared to control vehicle (p < 0.05). A similar trend was observed with the skin fibrometer.ADRC treatment promoted more normal collagen organization, improvement in the number of rete ridges (p < 0.01), longer elastic fiber length (p < 0.01), and reduced hypervascularity (blood vessel density; p < 0.05). ADRC treatment was associated with modulation of IL-6 expression within the wound/scar with upregulation 2 weeks after injury (wound healing phase) and downregulation at 2 months (early scarring phase) post-treatment compared to controlConclusionsThese findings support the potential therapeutic value of autologous ADRC administration for reduction of HTS development following deep-partial cutaneous injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0704-1) contains supplementary material, which is available to authorized users.

show abstract

“…Use of the ADRCs has also improved outcomes in patients with systemic sclerosis (53–56) and improved healing of thermal burns (57). Cytori Therapeutics is developing ADRCs for thermal burn injury, including burns that are complicated by radiation exposure, and these ADRCs improved healing of full thickness burns in minipigs exposed to a sub-lethal dose of total body irradiation (TBI) – a radiation combined injury (58). …”

Section: Meeting Program Overview4mentioning

confidence: 99%

Cellular Therapies for Treatment of Radiation Injury: Report from a NIH/NIAID and IRSN Workshop

et al. 2017

View full text Add to dashboard Cite

In recent years, there has been increasing concern over the possibility of a radiological or nuclear incident occurring somewhere in the world. Intelligence agencies frequently report that terrorist groups and rogue nations are seeking to obtain radiological or nuclear weapons of mass destruction. In addition, there exists the real possibility that safety of nuclear power reactors could be compromised by natural (such as the tsunami and subsequent Fukushima accident in Japan in March, 2011) or accidental (Three Mile Island, 1979 and Chernobyl, 1986) events. Although progress has been made by governments around the world to prepare for these events, including the stockpiling of radiation countermeasures, there are still challenges concerning care of patients injured during a radiation incident. Because the deleterious and pathological effects of radiation are so broad, it is desirable to identify medical countermeasures that can have a beneficial impact on several tissues and organ systems. Cellular therapies have the potential to impact recovery and tissue/organ regeneration for both early and late complications of radiation exposure. These therapies, which could include stem or blood progenitor cells, mesenchymal stromal cells (MSCs) or cells derived from other tissues (e.g., endothelium or placenta), have shown great promise in treating other nonradiation injuries to and diseases of the bone marrow, skin, gastrointestinal tract, brain, lung and heart. To explore the potential use of these therapies in the treatment of victims after acute radiation exposure, the National Institute of Allergy and Infectious Diseases cosponsored an international workshop in July, 2015 in Paris, France with the Institut de Radioprotection et de Sûreté Nucléaire. The workshop included discussions of data available from testing in preclinical models of radiation injury to different organs, logistics associated with the practical use of cellular therapies for a mass casualty incident, as well as international regulatory requirements for authorizing such drug products to be legally and readily used in such incidents. This report reviews the data presented, as well as key discussion points from the meeting.

show abstract

Development of a combined radiation and full thickness burn injury minipig model to study the effects of uncultured adipose-derived regenerative cell therapy in wound healing

Abstract: Although preliminary, this study provides a reproducible minipig model of thermal burn injury complicated by myelosuppressive total body irradiation that utilizes standardized procedures to evaluate novel countermeasures for potential use following attack by an improvised nuclear device.

Cited by 21 publications

References 33 publications

Efficacy of stem cell therapy for burn wounds: a systematic review and meta-analysis of preclinical studies

Efficacy of stem cell therapy for burn wounds: a systematic review and meta-analysis of preclinical studies

Autologous adipose-derived regenerative cell therapy modulates development of hypertrophic scarring in a red Duroc porcine model

Cellular Therapies for Treatment of Radiation Injury: Report from a NIH/NIAID and IRSN Workshop

Contact Info

Product

Resources

About