Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells Promotes Delayed Wound Healing in Diabetic Rats

Wan, Jing; Xia, Liulu; Liang, Wenjia; Liu, Yi; Cai, Qian

doi:10.1155/2013/647107

Cited by 72 publications

(61 citation statements)

References 44 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the host cells must be able to migrate and remodel their surroundings for the wound dressing to be effective. Thus the gel degradation rate should be kept within 40–50% over the course of 7 days [34]. …”

Section: Discussionmentioning

confidence: 99%

Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids

et al. 2017

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) secrete endogenous factors such as vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) that promote angiogenesis, modulate the inflammatory microenvironment, and stimulate wound repair, and MSC spheroids secrete more trophic factors than dissociated, individual MSCs. Compared to injection of cells alone, transplantation of MSCs in a biomaterial can enhance their wound healing potential by localizing cells at the defect site and upregulating trophic factor secretion. To capitalize on the therapeutic potential of spheroids, we engineered a fibrin gel delivery vehicle to simultaneously enhance the proangiogenic and anti-inflammatory potential of entrapped human MSC spheroids. We used multifactorial statistical analysis to determine the interaction between four input variables derived from fibrin gel synthesis on four output variables (gel stiffness, degradation rate, and secretion of VEGF and PGE2). Manipulation of the four input variables tuned fibrin gel biophysical properties to promote the simultaneous secretion of VEGF and PGE2 by entrapped MSC spheroids while maintaining overall gel integrity. MSC spheroids in stiffer gels secreted the most VEGF, while PGE2 secretion was highest in more compliant gels. Simultaneous VEGF and PGE2 secretion was greatest using hydrogels with intermediate mechanical properties, as small increases in stiffness increased VEGF secretion while maintaining PGE2 secretion by entrapped spheroids. The fibrin gel formulation predicted to simultaneously increase VEGF and PGE2 secretion stimulated endothelial cell proliferation, enhanced macrophage polarization, and promoted angiogenesis when used to treat a wounded three-dimensional human skin equivalent. These data demonstrate that a statistical approach is an effective strategy to formulate fibrin gel formulations that enhance the wound healing potential of human MSCs.

show abstract

Section: Discussionmentioning

confidence: 99%

Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In diabetic animal models, systemic or local injections, for example, of both MSCs promote angiogenesis and migration, and they have the ability to induce regeneration rather than fi brosis in the wound microenvironment. [94][95][96] . In human diabetic foot ulcers, implantation of autologous BM-MSCs signifi cantly improves clinical parameters such as ulcer size and pain-free walking distance [ 97 ] .…”

Section: Challenges and Perspectives In The Treatment Of Chronic Wounmentioning

confidence: 99%

Pathogenesis of wound healing disorders in the elderly

Makrantonaki

Wlaschek

Scharffetter‐Kochanek

2017

J Deutsche Derma Gesell

View full text Add to dashboard Cite

Summary The elderly constitute the age group most susceptible to wound healing disorders and chronic wounds, the most prevalent being venous leg ulcers, pressure ulcers, and diabetic foot ulcers. However, other age‐associated diseases should also be taken into consideration in the diagnostic workup of chronic wounds, and not be underestimated. A better understanding of the pathomechanisms involved in the wound healing process is of key importance in combatting the difficulties associated with the treatment of chronic wounds. In recent decades, considerable progress has been made in the development of pioneering therapeutic strategies for chronic wounds. In this context, the use of growth factors and cytokines, tissue engineering, and cell therapy – including stem cells – have proven very promising. Nevertheless, prior to their introduction into routine clinical practice, large controlled clinical trials are required to assess the safety of these techniques.

show abstract

“…Recent studies have outlined some successful approaches to promoting wound healing with MSCs, including autologous bone marrow-derived MSCs in fibrin matrix 52 or, more recently, intramuscular injection of autologous MSCs to improve diabetic wound closure. 54 While some trials have been aimed primarily at safety of MSC use for wound healing, 50 several clinical trials have shown the potential benefit of MSCs for inclusion in wound healing devices, including improved average rate of wound healing and general limb perfusion after treatment 53 and also improved acute wound healing correlating to the number of injected cells. 52 Despite any effects on healing, there was some doubt as to any reduction in limb amputation rate or relative pain levels among groups, a major consideration for effective therapy in chronic wounds.…”

Section: Chronic Skin Woundsmentioning

confidence: 99%