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The Role of Cellular Therapy in Wound Healing: Benefits and Limitations

Chronic non-healing wounds are those that do not undergo repair in a timely or predictable manner, posing immense challenges to wound care professionals, increasing pain and suffering to patients, and gobbling up healthcare resources around the world. This article discusses the use of various cellular therapies to improve wound healing outcomes in patients. 

Stem Cells and Wound Healing

Wound healing is a dynamic and complex physiological process occurring over multiple stages. Different cells responsible for inflammation, collagen production, angiogenesis, and keratin proliferation work together through the wound healing phases from inflammation to eventual contraction and remodeling. Research into the use of stem cells to promote faster healing of chronic wounds shows success. Stem cell-assisted therapy aids faster healing where the natural healing processes are not sufficient to prevent ischemia and tissue necrosis. Due to their proliferative potential as well as the ability to generate growth factors and chemo-cytokines necessary for wound healing, Endothelial progenitor cells (EPCs), Adipose-derived stem cells (ADSCs), and Bone marrow-derived mesenchymal cells (BMMSCs) are ideal. The following is a closer look at each of these therapies and their impact on wound healing.  

Endothelial progenitor cells (EPCs)

Human endothelial progenitor cells aid in the repair and revascularization of wounded or ischemic tissues. Studies indicate that EPCs derived from bone marrow may release growth factors and stimulate endothelialization following tissue injury or ischemia. EPCs also serve as diagnostic markers.  They promote neovascularization by invading and migrating within injured tissues and differentiating into mature endothelial cells guided by signals, including hypoxia, chemokines, and growth factors following injury. Based on the results of studies involving mice, transplantation of human CD133+ EPC into diabetic mice induced with streptozotocin enhanced the rate of wound healing and closure as well as the capillary density in granulation tissues. Another study found that the use of an EPC-conditioned medium improved vascularization in ischemic hindlimbs with no immune rejection. 

Bone marrow-derived mesenchymal cells (BMMSCs)

Mesenchymal stem cells obtained from the bone marrow are indicated for use in the area of chronic wound healing. Like endothelial progenitor cells, BMMSCs have the ability to differentiate into multiple cell types, including endothelial cells, hepatocytes, neural cells, keratinocytes, and fibrocytes. BMMSCs aid wound healing in chronic wounds, such as diabetic ulcers via cellular differentiation and the release of angiogenic growth factors, such as Angiopoietin-1 (Ang 1), Insulin-like growth factor 1 (IGF-1), epidermal growth factor (EGF), keratinocyte growth factor (KGF), and the vascular endothelial growth factor (VEGF). These qualities have also been found to enhance the wound contraction rate. However, the main drawback to the use of mesenchymal cells, such as BMMSCs is that they require invasive procedures. 

Adipose-derived stem cells (ADSC)

Research shows that mesenchymal stem cells derived from subcutaneous adipose tissues may help to improve healing outcomes in chronic wounds. ADSCs are more preferred over bone-marrow-derived stem cells in a host of regenerative therapies for two reasons: they are more easily harvested in large numbers with low morbidity and allow for non-invasive methods. When cultured in precise conditions, ADSCs can differentiate into multiple cell types necessary for optimal wound healing, e.g., vascular endothelial cells, adipocytes, chondrocytes, and myocytes. ADSCs also have anti-inflammatory, pro-angiogenesis, and anti-scarring effects that make them highly beneficial in wound care. In a 2009 research, ADSC transplantation showed a faster rate of healing, dermal closure, and increased perfusion in wounded mice tissues. ADSCs also secrete angiogenic growth factors, such as vascular endothelial growth factor (VEGF) necessary for inducing tissue regeneration. 

Limitations of Stem Cell Therapy for Wound Healing

Stem cell therapies using EPC, ADSC, and BMMSC cells remains a viable approach for treating chronic wounds, such as diabetic foot ulcers, and have shown significant success in clinical trials over the years. However, there are some limitations involved in the practice of tissue engineering. The use of endothelial progenitor cells (EPCs) has been correlated with the growth of tumors in patients. Bone-marrow-derived stem cells can also be hard to obtain from older patients, with impaired regenerative properties (proliferation and differentiation).