Scarless wound healing: Current insights from the perspectives of TGF-β, KGF-1, and KGF-2

The process of wound healing involves a complex and vast interplay of growth factors and cytokines that coordinate the recruitment and interaction of various cell types. A series of events involving inflammation, proliferation, and remodeling eventually leads to the restoration of the damaged tissue. Abrogation in the regulation of these events has been shown to result in excessive scarring or non-healing wounds. While the process of wound healing is not fully elucidated, it has been documented that the early events of wound healing play a key role in the outcome of the wound. Furthermore, high levels of inflammation have been shown to lead to scarring. The regulation of these events may result in scarless wound healing, especially in adults. The inhibition of transforming growth factor-β (TGF-β) and the administration of keratinocyte growth factors (KGF), KGF-1 and KGF-2, has in recent years yielded positive results in the acceleration of wound closure and reduced scarring. Here, we encapsulate recent knowledge on the roles of TGF-β, KGF1, and KGF2 in wound healing and scar formation and highlight the areas that need further investigation. We also discuss potential future directions for the use of growth factors in wound management.     

早期整形手术在深Ⅱ度烧伤患者治疗中的作用

为了探讨早期整形外科手术治疗对深Ⅱ度烧伤创面愈合后瘢痕挛缩畸形及功能障碍的影响,本研究选择深Ⅱ度烧伤患者60例作为研究对象,对患者进行早期功能性部位整形手术,其中研究组34例,对照组26例。对照组患者使用常规治疗和功能锻炼;研究组在对照组的基础上,使用瘢痕组织切除术、中厚皮肤移植术和术后功能锻炼,比较2组治疗后疗效的差异。研究结果表明,研究组34例烧伤患者接受整形手术后,各部位平均植皮成活率均达90%以上。术后第3个月和半年2组关节功能恢复效果不显著。研究组患者术后1年的关节功能恢复和疗效均显著优于对照组(p<0.05)。初步结论表明,研究组总有效率(100%)显著高于对照组(81.25%, p<0.05)。深Ⅱ度烧伤患者创面愈合后进行早期功能部位整形手术治疗能有效改善患处瘢痕挛缩导致的关节功能障碍。     

Fourier transform infrared evaluation of microscopic scarring in the cardiomyopathic heart: effect of chronic AT1 suppression

Our primary aim was to investigate the use of Fourier transform infrared (FTIR) spectromicroscopy as an accurate assay of cardiac extracellular matrix remodeling. Abnormal rearrangement or remodeling of the cardiac extracellular matrix is known to contribute to cardiac dysfunction. The microscopic multifocal necrosis and scarring are modulated by chronic AT(1) receptor blockade in experimental cardiomyopathy; thus, we also wished to rationalize the spectromicroscopic differences among control, untreated cardiomyopathic (CMP), and losartan-treated cardiomyopathic (LOS) hearts according to the pathogenesis of experimental cardiomyopathy. Male UM-X7.1 cardiomyopathic Syrian hamsters at early and late (65 and 200 days) stages of cardiomyopathy were subjected to 4-week losartan (15 mg/kg/day continuous infusion) treatment. Focal collagen microdomain distribution was confirmed spectroscopically by observation of the collagen IR fingerprint in the 1000-1800 cm(-1) region. Synchrotron FTIR spectromicroscopic map data were obtained from control (F1-beta strain) hamsters, nontreated cardiomyopathic, and losartan-treated CMP animals and imaged with mapping software, according to intensity of collagen fingerprint. Compared to controls, untreated late-stage CMP myocardium was characterized by elevated levels of fibrillar collagens and this was partially normalized with a 4-week losartan treatment. FTIR spectromicroscopy revealed that elevated collagen expression in focal microdomains is present in late-stage cardiomyopathy, and 4-week AT(1) blockade is associated with attenuation of collagen absorption in these lesions.     

Structure and function of the Arp2/3 complex

The Arp2/3 complex, a 220 kDa macromolecular assembly comprising two actin-related proteins and five other subunits, plays a key role in cellular motility by initiating the polymerization of new actin filaments. Crystal and cryo-electron microscopic structures of the Arp2/3 complex and branch junctions have clarified extensive biochemical data on the mechanism of this process.     

Learning from regeneration research organisms: The circuitous road to scar free wound healing

The skin is the largest organ in the body and plays multiple essential roles ranging from regulating temperature, preventing infection and ultimately defining who we are physically. It is a highly dynamic organ that constantly replaces the outermost cells throughout life. However, when faced with a major injury, human skin cannot restore a significant lesion to its original functionality, instead a reparative scar is formed. In contrast to this, many other species have the unique ability to regenerate full thickness skin without formation of scar tissue. Here we review recent advances in the field that shed light on how the skin cells in regenerative species react to injury to prevent scar formation versus scar forming humans.     

Fibroblast sources: Where can we get them?

Fibroblasts are cells widely used in cell culture, both for transient primary cell culture or permanent as transformed cell lines. Lately, fibroblasts become cell sources for use in disease modeling after cell reprogramming because it is easily accessible in the body. Fibroblasts in patients will maintain all genetic background during reprogramming into induced pluripotent stem cells. In spite of their large use, fibroblasts are obtained after an invasive procedure, a superficial punch skin biopsy, collected under patient’s local anesthesia. Taking into consideration the minimum patient’s discomfort during and after the biopsy procedure, as well as the aesthetics aspect, it is essential to reflect on the best site of the body for the biopsy procedure combined with the success of getting robust fibroblast cultures in the lab. For this purpose, we compared the efficiency of four biopsy sites of the body (skin from eyelid, back of the ear, abdominal cesarean scar and groin). Cell proliferation assays and viability after cryopreservation were measured. Our results revealed that scar tissue provided fibroblasts with higher proliferative rates. Also, fibroblasts from scar tissues presented a higher viability after the thawing process.     

子宫动脉化疗栓塞与单子宫动脉栓塞在瘢痕妊娠治疗有效性对比

目的:对比子宫动脉化疗栓塞与单子宫动脉栓塞在瘢痕妊娠治疗中的有效性。方法:选择2016年1月-2018年12月在我院诊治的瘢痕妊娠患者96例,根据手术方式不同分为两组,各48例,其中,对照组采用单子宫动脉栓塞治疗,研究组采用子宫动脉化疗栓塞治疗,记录并对比两组术中出血量、手术时间、住院时间、人绒毛膜促性腺激素β亚单位(human chorionic gonadotrop(h)in-beta subunit,β-HCG)下降至正常范围时间、宫腔异常包块消失时间、月经恢复正常时间、首次肛门排气时间等指标;记录并对比两组患者治疗前后的卵泡刺激素(follicle stimulating hormone,FSH)、黄体生成素(luteinizing hormone,LH)、雌二醇(estradiol,E2)、抑制素B(inhibin B,INHB)等卵巢功能指标变化;记录并对比两组的膀胱损伤、阴道流血、感染等术后并发症的发生情况。结果:研究组的术中出血量、手术时间、住院时间均显著少于(短于)对照组(P0.05);研究组的β-HCG下降至正常范围时间、宫腔异常包块消失时间、月经恢复正常时间、首次肛门排气时间均显著短于对照组(P0.05);治疗前,两组的FSH、LH、E2、INHB等卵巢功能指标对比均无显著性差异(P0.05);治疗后,两组的FSH水平均升高,LH、E2、INHB水平均降低,且研究组更优(P0.05);研究组的并发症发生率显著低于对照组(6.25%vs. 20.83%,P0.05)。结论:相比于单子宫动脉栓塞,子宫动脉化疗栓塞有利于改善瘢痕妊娠患者的手术相关指标及术后恢复情况,对患者卵巢功能的恢复较好,且安全性较高,值得推荐至临床广泛应用。     

瘢痕子宫再次住院妊娠不同分娩方式的研究

目的:探讨瘢痕子宫妇女再次妊娠后采用不同分娩方式的临床效果,为今后瘢痕子宫产妇分娩提供可靠经验和指导.方法:选择从2011年5月至2012年10月在我院门诊检查并收住入院的120例瘢痕子宫再次妊娠孕妇,将120例再次妊娠产妇平均分为两组,分别是剖宫产组和阴道分娩组,对比两组孕妇产后新生儿窒息情况、产后出血及产后发热等情况.结果:通过统计后发现采用剖宫产组产妇在平均产后出血量、新生儿窒息等方面与阴道分娩组差异不大,但和初产妇剖宫产之间差距较多.结论:瘢痕子宫妇女再次妊娠后可以采用阴道分娩方式分娩,在分娩前后做好准备工作和产妇心理疏导,值得临床使用.     

Transplantation of mature adipocyte-derived dedifferentiated fat cells promotes locomotor functional recovery by remyelination and glial scar reduction after spinal cord injury in mice

Mature adipocyte-derived dedifferentiated fat cells (DFAT) have a potential to be useful as new cell-source for cell-based therapy for spinal cord injury (SCI), but the mechanisms remain unclear. The objective of this study was to examine whether DFAT-induced functional recovery is achieved through remyelination and/or glial scar reduction in a mice model of SCI. To accomplish this we subjected adult female mice (n = 22) to SCI. On the 8th day post-injury locomotor tests were performed, and the mice were randomly divided into two groups (control and DFAT). The DFAT group received stereotaxic injection of DFAT, while the controls received DMEM medium. Functional tests were conducted at repeated intervals, until the 36th day, and immunohistochemistry or staining was performed on the spinal cord sections. DFAT transplantation significantly improved locomotor function of their hindlimbs, and promoted remyelination and glial scar reduction, when compared to the controls. There were significant and positive correlations between promotion of remyelination or/and reduction of glial scar, and recovery of locomotor function. Furthermore, transplanted DFAT expressed markers for neuron, astrocyte, and oligodendrocyte, along with neurotrophic factors, within the injured spinal cord. In conclusion, DFAT-induced functional recovery in mice after SCI is probably mediated by both cell-autonomous and cell-non-autonomous effects on remyelination of the injured spinal cord.     

Transmural “Scar-to-Scar” Reentrant Ventricular Tachycardia

We describe a scar-related reentrant ventricular tachycardia circuit with a proximal segment in an endocardial basal septal scar and an exit in a region of slow conduction in a non-overlapping region of epicardial basal lateral scar. The 12-lead EKG demonstrates criteria for a basal lateral epicardial VT, however the same morphology could be produced with a longer stim-latency with pace mapping or VT induction from the endocardial septal region of scar. A significant segment of myocardium demonstrated no endocardial or epicardial scar on electroanatomic mapping, suggesting the presence of a mid-myocardial isthmus. Further evidence was provided by assessment of unipolar settings. The epicardial VT that initially appeared to originate from the basal lateral epicardial region, was successfully treated with radiofrequency ablation of the lateral aspect of the endocardial septal scar.