Genetically-modified bone mesenchymal stem cells with TGF-β 3 improve wound healing and reduce scar tissue formation in a rabbit model

Abstract Background Hematopoietic stem cells(HSCs) and mesenchymal stem cells(MSCs) can participate in wound healing. However, very few studies had shown HSCs and MSCs could arrive to the wound and differentiate into tissues. In this study, we intend to investigate the role of bone marrow HSCs and MSCs in wound healing. Methods We first removed the bone marrow of mice by irradiation. Furthermore, we injected different colours of fluorescent HSCs and MSCs into the tail vein of irradiated mice to reconstruct bone marrow function. We prepared wound models on the back of these mice. In vivo imaging and immunohistochemical staining were used to track the expression of fluorescent protein. Results HSCs and MSCs have been isolated and cultured. HSCs expressed expressed Sca1, not lineage, CD34 or CD48. MSCs expressed expressed CD29 and CD44,not CD34 or CD45. HSCs labeled with green fluorescent protein reached the wound and co-expressed with desmin and α-SMA. MSCs didn’t stay on the wound. Conclusions The results show HSCs in the bone marrow of mice can directly participate in wound healing and differentiate into pericytes and myofibroblasts.

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Genetically Modified Porcine Mesenchymal Stem Cells by Lentiviral Tbx18 Create a Biological Pacemaker

Stem Cells International ◽

10.1155/2019/3621314 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Yannan Hu ◽

Ning Li ◽

Liang Liu ◽

Hao Zhang ◽

Xiang Xue ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Right Ventricle ◽

Large Scale ◽

Genetically Modified ◽

Pacemaker Activity ◽

Bone Mesenchymal Stem Cells ◽

The Right ◽

Biological Pacemaker

Background. Tbx18 is a vital transcription factor involved in embryonic sinoatrial node (SAN) formation process but is gradually vanished after birth. Myocardial injection of lentiviral Tbx18 converts cardiomyocytes into pacemaker-like cells morphologically and functionally. In this in vitro and in vivo study, genetical modification of porcine bone mesenchymal stem cells (BMSCs) by recapturing the Tbx18 expression creates a biological pacemaker which was examined. Methods. The isolated porcine BMSCs were transfected with lentiviral Tbx18, and the induced pacemaker-like cells were analyzed using real-time polymerase chain reaction and western blotting to investigate the efficiency of transformation. Then, the induced pacemaker-like cells were implanted into the right ventricle of the SAN dysfunction porcine model after the differentiation process. Biological pacemaker activity and ectopic pacing region were tested by an electrocardiograph (ECG) monitor. Results. The isolated porcine BMSCs expressed specific surface markers of stem cells; meanwhile, the expression of myocardial markers was upregulated significantly after lentiviral Tbx18 transfection. The porcine SAN dysfunction model was constructed by electrocoagulation using a surgical electrotome. The results showed that the mean heart beat (HR) of BMSCs-Tbx18 was significantly higher than that of BMSCs-GFP. An ectopic pacing region was affirmed into the right ventricle by ECG after implantation of BMSCs-Tbx18. Conclusion. It was verified that Lenti-Tbx18 is capable of transducing porcine BMSCs into pacemaker-like cells. Genetically modified porcine BMSCs by lentiviral Tbx18 could create a biological pacemaker. However, further researches in large-scale animals are required to rule out unexpected complications prior to application in clinical practice.

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Fibroblast migration and collagen deposition during dermal wound healing: mathematical modelling and clinical implications

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2006.1773 ◽

2006 ◽

Vol 364 (1843) ◽

pp. 1385-1405 ◽

Cited By ~ 139

Author(s):

Steven McDougall ◽

John Dallon ◽

Jonathan Sherratt ◽

Philip Maini

Keyword(s):

Wound Healing ◽

Diffusion Coefficient ◽

Scar Tissue ◽

Tissue Formation ◽

Collagen Deposition ◽

Dermal Wound Healing ◽

Fibroblast Migration ◽

Collagen Alignment ◽

Dermal Wound ◽

Scar Tissue Formation

The extent to which collagen alignment occurs during dermal wound healing determines the severity of scar tissue formation. We have modelled this using a multiscale approach, in which extracellular materials, for example collagen and fibrin, are modelled as continua, while fibroblasts are considered as discrete units. Within this model framework, we have explored the effects that different parameters have on the alignment process, and we have used the model to investigate how manipulation of transforming growth factor-β levels can reduce scar tissue formation. We briefly review this body of work, then extend the modelling framework to investigate the role played by leucocyte signalling in wound repair. To this end, fibroblast migration and collagen deposition within both the wound region and healthy peripheral tissue are considered. Trajectories of individual fibroblasts are determined as they migrate towards the wound region under the combined influence of collagen/fibrin alignment and gradients in a paracrine chemoattractant produced by leucocytes. The effects of a number of different physiological and cellular parameters upon the collagen alignment and repair integrity are assessed. These parameters include fibroblast concentration, cellular speed, fibroblast sensitivity to chemoattractant concentration and chemoattractant diffusion coefficient. Our results show that chemoattractant gradients lead to increased collagen alignment at the interface between the wound and the healthy tissue. Results show that there is a trade-off between wound integrity and the degree of scarring. The former is found to be optimized under conditions of a large chemoattractant diffusion coefficient, while the latter can be minimized when repair takes place in the presence of a competitive inhibitor to chemoattractants.

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