Feasibility of Autologous Adipose-derived Stromal Cells from Stromal Vascular Fraction (SVF) to Treat Adults with Pressure Ulcers or Diabetic Foot Ulcers

Overview

About this study

Determine safety and feasibility of using institutionally prepared autologous, uncultured SVF on patients with Stage III  pressure ulcers or Stage 1 or 2 diabetic foot ulcers.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Adults greater than 18 years old.
  • Males and females.
  • Stage III pressure ulcers measuring 5 cc – 36 cc in volume (as measured by filling the wound with Normal Saline).
  • Inpatient or outpatient treatment of pressure ulcers.
  • Diabetic Foot Ulcer Stage 1 or 2 of any size.
  • Co-morbidities may include:
    • Peripheral Vascular Disease (PVD);
    • Using Rutherford Scale: Stage 0-4 will be included;  
    • Stage 0 – Asymptomatic;
    • Stage 1 – Mild claudication;
    • Stage 2 – Moderate claudication; The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters.
    • Stage 3 – Severe claudication
    • Stage 4 – Rest pain
    • Stage 5 – Ischemic ulceration not exceeding ulcer of the digits of the foot;
    • Stage 6 – Severe ischemic ulcers or frank gangrene;
    • Coronary Artery Disease (CAD);
    • Chronic Renal Disease (CRD);
    • Can be stages 1-5 (and based on clinical judgment of the physician);
    • Chronic Liver Disease (CLD);
    • MELD* score  < 11;
    • Hypertension (HTN);
    • Normal, Prehypertensive, Hypertensive Stage 1 and 2 are included.  Hypertensive crisis (>180/ >110mmHg) is excluded from the study and subject may be re-eligible when adequate BP control is maintained.
    • Diabetes;
    • HbA1c < 9.
  • The ability of subjects to give appropriate consent or have an appropriate representative available to do so.
  • The ability of subjects to return for weekly wound assessments.

Exclusion Criteria:

  • Patients with allergies to TISSEEL, Tegaderm, or silicon.
  • Diabetics with poor glucose metabolic control exhibited by an HbA1c > 9.
  • Target wounds that are in close proximity to potential cancerous lesions.
  • Patients who require Negative Pressure Wound Therapy (NPWT), limb amputation, or surgical intervention at the target wound at the time of screening.
  • Wounds located on the face.
  • Patients with Stage 5 or 6 Peripheral Vascular disease (specifically, wounds that are caused by peripheral vascular disease such as leg ulcers).
  • Osteomyelitis of the side (Ipsilateral limb) of the treated wound.
  • Wound abscess.
  • BMI of < 16.
  • Clinical signs of critical colonization or local infection.
  • Pregnancy.
  • Prolonged (> 6 months) use of steroids.
  • Patients on active regimen of chemotherapy.
  • Patients receiving radiation in proximity of wound.
  • Decompensated chronic liver disease; i.e., patients who have experienced hepatic encephalopathy, ascites,  bleeding due to portal hypertension and jaundice or in patients with chronic liver disease with a Model for End-stage Liver Disease (MELD) scores > 11 will not be included.
  • End of life.

Eligibility last updated 12/7/21. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Houssam Farres, M.D.

Open for enrollment

Contact information:

Mauricia Buchanan R.N.

Buchanan.Mauricia@mayo.edu

More information

Publications

  • Non-revascularizable critical limb ischemia (CLI) is the most severe stage of peripheral arterial disease, with no therapeutic option. Extensive preclinical studies have demonstrated that adipose-derived stroma cell (ASC) transplantation strongly improves revascularization and tissue perfusion in ischemic limbs. This study, named ACellDREAM, is the first phase I trial to evaluate the feasibility and safety of intramuscular injections of autologous ASC in non-revascularizable CLI patients. Read More on PubMed
  • Critical Limb Ischemia (CLI) is the most advanced stage of peripheral arterial disease and is usually treated with bypass surgery or endovascular revascularization. However, a considerable proportion of CLI patients are not eligible to these treatment strategies and amputation is often the only option left. In the past decade, research has focused on bone marrow (BM)-derived cell-based strategies that aim at neovascularization to improve limb perfusion. Individual studies did not convincingly prove efficacy of BM-derived cell therapy in CLI patients thus far. Read More on PubMed
  • Fibrin glue has been widely investigated as a cell delivery vehicle for improving the therapeutic effects of mesenchymal stem cells (MSCs). Implanted MSCs produce their therapeutic effects by secreting paracrine factors and by replacing damaged tissues after differentiation. While the influence of fibrin glue on the differentiation potential of MSCs has been well documented, its effect on paracrine function of MSCs is largely unknown. Herein we investigated the influence of fibrin glue on the paracrine effects of MSCs. MSCs were isolated from human adipose tissue. The effects of fibrin glue on survival, migration, secretion of growth factors, and immune suppression of MSCs were investigated in vitro. MSCs in fibrin glue survived and secreted growth factors such as the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) over 14 days. VEGF and immune modulators, including the transforming growth factor (TGF)-β1 and prostaglandin E2, secreted from MSCs in fibrin glue significantly increased under inflammatory conditions. Thus, MSCs in fibrin glue effectively suppressed immune reactions. In addition, fibrin glue protected the MSCs from oxidative stress and prevented human dermal fibroblast death induced by exposure to extreme stress. In contrast, MSCs within fibrin glue hardly migrated. These results suggest that fibrin glue may sustain survival of implanted MSCs and their paracrine function. Our results provide a mechanistic data to allow further development of MSCs with fibrin glue as a clinical treatment. Read More on PubMed
  • Adipose tissue is a rich and very convenient source of cells for regenerative medicine therapeutic approaches. However, a characterization of the population of adipose-derived stromal and stem cells (ASCs) with the greatest therapeutic potential remains unclear. Under the authority of International Federation of Adipose Therapeutics and International Society for Cellular Therapy, this paper sets out to establish minimal definitions of stromal cells both as uncultured stromal vascular fraction (SVF) and as an adherent stromal/stem cells population. Read More on PubMed
  • Adipose tissue represents a practical source of autologous mesenchymal stromal cells (MSCs) and vascular-endothelial progenitor cells, available for regenerative therapy without in vitro expansion. One of the problems confronting the therapeutic application of such cells is how to immobilize them at the wound site. We evaluated in vitro the growth and differentiation of human adipose stromal vascular fraction (SVF) cells after delivery through the use of a fibrin spray system. Read More on PubMed
  • This review provides a thorough and clear discussion on the outcomes of stem cells in treating chronic wounds. With recent technological developments that now allow isolation and culture of stem cells, researchers are able to perform vigorous studies on somatic or adult stem cells. Human and animal stem cell studies are discussed with a focus on the basic process of stem cells in wound healing and the authors' first-hand clinical experience with stem cells used for chronic wound healing. Read More on PubMed
  • To identify better cells for the treatment of diabetic critical limb ischemia (CLI) and foot ulcer in a pilot trial. Read More on PubMed
  • Nonhealing wounds remain a significant challenge for plastic surgeons. More than 600,000 people suffer from venous ulcers and 1.5 to 3 million people are being treated for pressure sores every year in the United States. The use of tissue engineering techniques such as stem-cell therapy and gene therapy to improve wound healing is a promising strategy. Adipose tissue represents a source of cells that may be able to enhance wound healing. Adipose-derived stem cells (ASCs) are adult stem cells that are easily harvested and of great interest for plastic surgeons. Specifically, ASCs secrete angiogenic growth factors that can induce tissue regeneration. This review describes innovative research strategies using ASCs therapies for treatment of chronic, nonhealing wounds. Read More on PubMed
  • Pressure ulcers are especially difficult to treat in patients with spinal cord injury (SCI) and recurrence rates are high. Prompted by encouraging results obtained using bone marrow stem cells to treat several diseases including chronic wounds, this study examines the use of autologous stem cells from bone marrow to promote the healing of pressure ulcers in patients with SCI. Read More on PubMed
  • To identify the impact of pressure ulcers (PUs) and PU interventions on health-related quality of life (HRQL). Read More on PubMed
  • The nonhematopoietic component of bone marrow includes multipotent mesenchymal stem cells (MSC) capable of differentiating into fat, bone, muscle, cartilage, and endothelium. In this report, we describe the cell culture and characterization, delivery system, and successful use of topically applied autologous MSC to accelerate the healing of human and experimental murine wounds. A single bone marrow aspirate of 35-50 mL was obtained from patients with acute wounds (n = 5) from skin cancer surgery and from patients with chronic, long-standing, nonhealing lower extremity wounds (n = 8). Cells were grown in vitro under conditions favoring the propagation of MSC, and flow cytometry and immunostaining showed a profile (CD29+, CD44+, CD105+, CD166+, CD34-, CD45-) highly consistent with published reports of human MSC. Functional induction studies confirmed that the MSC could differentiate into bone, cartilage, and adipose tissue. The cultured autologous MSC were applied up to four times to the wounds using a fibrin polymer spray system with a double-barreled syringe. Both fibrinogen (containing the MSC) and thrombin were diluted to optimally deliver a polymerized gel that immediately adhered to the wound, without run-off, and yet allowing the MSC to remain viable and migrate from the gel. Sequential adjacent sections from biopsy specimens of the wound bed after MSC application showed elongated spindle cells, similar to their in vitro counterparts, which immunostained for MSC markers. Generation of new elastic fibers was evident by both special stains and antibodies to human elastin. The application of cultured cells was safe, without treatment-related adverse events. A strong direct correlation was found between the number of cells applied (greater than 1 x 10(6) cells per cm2 of wound area) and the subsequent decrease in chronic wound size (p = 0.0058). Topical application of autologous MSC also stimulated closure of full-thickness wounds in diabetic mice (db/db). Tracking of green fluorescent protein (GFP)+ MSC in mouse wounds showed GFP+ blood vessels, suggesting that the applied cells may persist as well as act to stimulate the wound repair process. These findings indicate that autologous bone marrow-derived MSC can be safely and effectively delivered to wounds using a fibrin spray system. Read More on PubMed
  • There is evidence that stem cells contribute to the restoration of tissue vascularization and organ function. The objective of this study was to assess the presence of adipose-derived adult stem cells left in their natural scaffold in the purified lipoaspirate and to assess the clinical effectiveness of lipoaspirate transplantation in the treatment of radiation side effects. Read More on PubMed
  • To identify the independent effect of pressure ulcers on excess length of stay and control for all observable factors that may also contribute to excess length of stay. Hospitalized patients who develop a pressure ulcer during their hospital stay are at a greater risk for increased length of stay as compared with patients who do not. Read More on PubMed
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CLS-20144029

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