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Review
. 2021 Jul;41(4):2130-2171.
doi: 10.1002/med.21789. Epub 2021 Feb 1.

Adipose-derived stromal cells for nonhealing wounds: Emerging opportunities and challenges

Affiliations
Review

Adipose-derived stromal cells for nonhealing wounds: Emerging opportunities and challenges

Milena Deptuła et al. Med Res Rev. 2021 Jul.

Abstract

Wound healing complications affect thousands of people each year, thus constituting a profound economic and medical burden. Chronic wounds are a highly complex problem that usually affects elderly patients as well as patients with comorbidities such as diabetes, cancer (surgery, radiotherapy/chemotherapy) or autoimmune diseases. Currently available methods of their treatment are not fully effective, so new solutions are constantly being sought. Cell-based therapies seem to have great potential for use in stimulating wound healing. In recent years, much effort has been focused on characterizing of adipose-derived mesenchymal stromal cells (AD-MSCs) and evaluating their clinical use in regenerative medicine and other medical fields. These cells are easily obtained in large amounts from adipose tissue and show a high proregenerative potential, mainly through paracrine activities. In this review, the process of healing acute and nonhealing (chronic) wounds is detailed, with a special attention paid to the wounds of patients with diabetes and cancer. In addition, the methods and technical aspects of AD-MSCs isolation, culture and transplantation in chronic wounds are described, and the characteristics, genetic stability and role of AD-MSCs in wound healing are also summarized. The biological properties of AD-MSCs isolated from subcutaneous and visceral adipose tissue are compared. Additionally, methods to increase their therapeutic potential as well as factors that may affect their biological functions are summarized. Finally, their therapeutic potential in the treatment of diabetic and oncological wounds is also discussed.

Keywords: SVF; adipose-derived stromal cells; chronic wounds; diabetic ulcers; fat transfer; oncological wounds; wound healing.

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Figures

Figure 1
Figure 1
Wound healing process in acute and chronic wounds [Color figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
Chronic wounds of different etiology. (A) Posttraumatic chronic wound of lateral ankle, diabetic foot syndrome; (B) Postoperative wound of abdomen, operation of hernia in postoperative scar complicated by infection and necrosis of the abdominal wall, (C) Posttraumatic chronic wound of shank, ischemic wound [Color figure can be viewed at wileyonlinelibrary.com]
Figure 3
Figure 3
Skin complications in oncological patients. (A) 57‐year‐old patient after a radical mastectomy and postoperative radiotherapy due to breast cancer. The figure shows skin discoloration in the irradiated area, that is, at the breast and armpit. In the postoperative course, features of marginal necrosis of the wound treated in an outpatient setting were observed; (B) 35‐year‐old patient after a radical surgery of soft tissues sarcoma of a right lower leg above the ankle and a postoperative radiotherapy. Due to ischemia, the wound in the lower limb, in the area from the back and below the ankle, was accompanied by prolonged healing. The figure shows the place of impaired healing visible as a depression with a fragment of an atrophic wound (arrow); (C) 47‐year‐old patient with the ulceration of the back (dimensions:17 ×10 cm) resulting from skin cancer before the radical procedure. This type of neoplastic ulcer is associated with infection and necrosis. During radical surgery, the most important element is to protect the operated site from infection of the postoperative wound. The arrow marks the site of ulceration as a place with increased risk of postoperative wound infection; (D) Tissue loss of the left tight in a 63‐year‐old patient after a radical surgery of soft tissues sarcoma and postoperative radiotherapy. A fragment of the thigh bone with a defect in the thigh muscles is visible. It is the most difficult variant to heal, due to the extensive tissue loss and the condition after undergoing oncological treatment. The arrow marks the exposed femur [Color figure can be viewed at wileyonlinelibrary.com]
Figure 4
Figure 4
Fat collection through surgical resection. (A, 1) Collection of subcutaneous adipose tissue. Visualization of surgical wound during the process of fat tissue sample collection from subcutaneous tissue. Arrow points at the base of the wound which consists of fascial tissue of abdominal wall. (A, 2) Collection of visceral adipose tissue. Visualization of surgical wound after laparotomy procedure. The fat tissue sample is collected from the round ligament of the liver, arrow points at round ligament of the liver. (B, 1) Subcutaneous adipose tissue. (B, 2) Visceral adipose tissue. The photo shows intraperitoneal adipose tissue, the fragment is coated with the serosa (arrow) [Color figure can be viewed at wileyonlinelibrary.com]
Figure 5
Figure 5
Isolation of AD‐MSCs by enzymatic method. AD‐MSC, adipose‐derived mesenchymal stromal cell [Color figure can be viewed at wileyonlinelibrary.com]
Figure 6
Figure 6
Fat grafting by Coleman technique. (A) Infiltration cannula; (B) Harvesting canula; (C) Fat transfer canula; (D) Syringe for fat harvesting connected with insulin syringe for fat transfer with a Luer‐ Lock connector; (E) Harvesting fat tissue—Coleman technique; (F) Lipoaspirate; (G) Autologous fat grafting into the chronic wound (our preliminary trials in patients, approved by the Independent Bioethics Commission for Research of the Medical University of Gdansk—permission number NKBBN/707/2018‐2019) [Color figure can be viewed at wileyonlinelibrary.com]

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