New advances in the mesenchymal stem cells therapy against skin flaps necrosis

Mesenchymal stem cells(MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various cells, such as osteoblasts, adipocytes, chondrocytes, vascular endothelial progenitor cells, and other cell types. MSCs are being widely studied as potential cell therapy agents due to their angiogenic properties, which have been well established by in vitro and in vivo researches. Within this context, MSCs therapy appears to hold substantial promise, particularly in the treatment of conditions involving skin grafts, pedicle flaps, as well as free flaps described in literatures. The purpose of this review is to report the new advances and mechanisms underlying MSCs therapy against skin flaps necrosis.

Epidermal stem cells and skin tissue engineering in hair follicle regeneration

The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge stillpending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients' psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide threedimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This field is attractive not only to academic researchers but also to the companies that own almost half of the patents in this field.

Vital roles of stem cells and biomaterials in skin tissue engineering

Tissue engineering essentially refers to technology for growing new human tissue and is distinct from regenerative medicine. Currently, pieces of skin are already being fabricated for clinical use and many other tissue types may be fabricated in the future.Tissue engineering was first defined in 1987 by the United States National Science Foundation which critically discussed the future targets of bioengineering research and its consequences. The principles of tissue engineering are to initiate cell cultures in vitro, grow them on scaffolds in situ and transplant the composite into a recipient in vivo. From the beginning, scaffolds have been necessary in tissue engineering applications. Regardless, the latest technology has redirected established approaches by omitting scaffolds. Currently, scientists from diverse research institutes are engineering skin without scaffolds. Due to their advantageous properties, stem cells have robustly transformed the tissue engineering field as part of an engineered bilayered skin substitute that will later be discussed in detail. Additionally, utilizing biomaterials or skin replacement products in skin tissue engineering as strategy to successfully direct cell proliferation and differentiation as well as to optimize the safety of handling during grafting is beneficial. This approach has also led to the cells' application in developing the novel skin substitute that will be briefly explained in this review.

Improvement of Atrophic Acne Scar and Skin Complexity by Combination of Aqueous Human Placenta Extract and Mesenchymal Stem Cell Mesotherapy

Atrophic scars, a permanent complication of severe acne, have negative effect on psychology in adolescent. The treatment of atrophic scar is depended on types of scar and it is difficult to improve by a single treatment. Mesenchymal stem cell is a scientific approval for surgery scar treatment and wound healing. We present a case report of female presented with atrophic acne scar distributed on both cheeks. The case aims to prove that the combination of MSCs and aqueous human placenta extract (RGF&#174) contained bioactive therapeutic molecules obviously promoted the improvement of skin scar to reach the optimal outcomes. We first found that MSCs-contained human placenta extract solution combination subcision improves the atrophic acne scar and skin complexity by enhancement of skin cell regeneration.

Constructing skin-equivalents using hair follicle stem cells

Objective： To establish the method of constructing skin-equivalents （SE） using hair follicle stem cells （HFSC）. Methods： K19 positive cells derived from hair were cultivated using serum-free medium KGM and seeded on dermal equivalents （DE）. After the culture between the air-liquid interface for 14 days, SE were harvested and used for evaluation. Results： K19 positive cells chosen as HFSC were located in bulge of out root sheet in hair follicle. Cultivated HFSC could build a fully developed, multi-layered epidermis on the basis of DE, resembling the skin structure. Conclusion： HFSC located in out root sheet can differentiate into kerafinocyte in vitro and be used for SE construction.

Skin Disinfection with 2% Chlorine Gluconate-Adine in Autologous Peripheral Hematopoietic Stem Cell Transplantation Patients

Background: Autologous peripheral blood hematopoietic stem cell transplantation is widely used in the treatment of malignant lymphoma. Patients are prone to infection during the transplantation immune deficiency period. There has been a lot of clinical research into how to better manage this period of vulnerability. Objective: This study aims to investigate the efficacy of 2% chlorhexidine gluconate (CHG) for skin disinfection in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) and observe any adverse reactions. Methods: A total of 106 patients receiving autologous hematopoietic stem cell transplantation from November 2019 to December 2020 in our district were selected as the control group. From January 2021 to January 2022, 106 patients with autologous hematopoietic stem cells were included in the experimental group. The control group used the immersion bath method. The experimental group was treated with an improved scrub bath method (including 3M 2% chlorhexidine gluconate medical sanitary wipes to wipe the whole skin once). Results: The bacteria-carrying rate of the improved method (37.74%) was significantly better than that of the traditional soaking method (72.64%), and the difference was statistically significant (P Conclusion: The improved bath/wipe method has a significant positive effect on skin disinfection for patients undergoing HSCT.

Follicle and melanocyte stem cells, and their application in neuroscience A Web of Science-based literature analysis

OBJECTIVE： To identify global research trends of follicle and melanocyte stem cells, and their application in neuroscience. DATA RETRIEVAL： We performed a bibliometric analysis of studies from 2002 to 2011 on follicle and melanocyte stem cells, and their application in neuroscience, which were retrieved from the Web of Science, using the key words follicle stem cell or melanocyte stem cell, and neural, neuro or nerve. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed published articles on follicle and melanocyte stem cells, and their application in neuroscience, which were indexed in the Web of Science; （b） original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） documents that were not published in the public domain; and （c） a number of corrected papers from the total number of articles. MAIN OUTCOME MEASURES： （1） Distribution of publications on follicle and melanocyte stem cells by years, journals, countries, institutions, institutions in China, and most cited papers. （2） Distribution of publications on the application of follicle and melanocyte stem cells in neuroscience by years, journals, countries, institutions, and most cited papers. RESULTS： Of the 348 publications from 2002 to 2011 on follicle and melanocyte stem cells, which were retrieved from the Web of Science, more than half were from American authors and institutes. The most prolific institutions in China for publication of papers on follicle and melanocyte stem cells were the Fourth Military Medical University and Third Military Medical University. The most prolific journals for publication of papers on follicle and melanocyte stem cells were the Journal of Investigative Dermatology, Pigment Cell ＆ Melanoma Research. Of the 63 publications from 2002 to 2011 on the application of follicle and melanocyte stem cells in neuroscience, which were retrieved from the Web of Science, more than half were from American authors and institutes, and no papers were from Chinese authors and institutes. The most prolific journals for publication of papers on the application of follicle and melanocyte stem cells in neuroscience were the Journal of Investigative Dermatology, Pigment Cell ＆ Melanoma Research. CONCLUSION： Based on our analysis of the literature and research trends, we found that follicle stem cells might offer further benefits in neural regenerative medicine.

Epithelial stem cell islands in the regenerated epidermis

Objective: The effects of growth factors on wound healing have been studied extensively, however, their molecular and genetic mechanisms that regulate epidermal regeneration are not fully understood. In this study, we explore the cell reversion characteristics and epithelial stem cell distribution in human regenerated epidermis treated with recombinant human epidermal growth factor (rhEGF). Methods:Tissue biospies from 8 regenerated skins treated with rhEGF were used to evaluate the cell reversion.

Role of adipose-derived stromal cells in pedicle skin flap survival in experimental animal models

The use of skin flaps in reconstructive surgery is the first-line surgical treatment for the reconstruction of skin defects and is essentially considered the starting point of plastic surgery. Despite their excellent usability, their application includes general surgical risks or possible complications, the primary and most common is necrosis of the flap. To improve flap survival, researchers have used different methods, including the use of adiposederived stem cells, with significant positive results. In our research we will report the use of adipose-derived stem cells in pedicle skin flap survival based on current literature on various experimental models in animals.

Local Cutaneous Effects Associated with Chlorhexidine-Impregnated Gel Dressing in Hematopoietic Stem Cell Transplantation Patients

Introduction: Hematopoietic stem cell transplantation (HSCT) often requires a central venous catheter (CVC) for quick and safe vascular access. Currently, new technologies are available to protect the catheter insertion site, such as chlorhexidine-impregnated gel dressings (CIGD). Objectives: To evaluate local cutaneous effects associated with CIGD in patients undergoing HSCT. Methods: In this cross-sectional, prospective study, we evaluated 25 HSCT patients who had a CVC inserted. Patients were visited daily to monitor the CIGD changing procedures and evaluate abnormalities of the underlying skin after dressing removal. Findings: Local erythema was the most frequently detected abnormality, although usually transient and considered secondary to the mechanical trauma of dressing removal. The most severe lesions, consisting of areas of skin loss, erythematous plaques and/or vesicles were classified as skin irritation and presented in 11 (44%) of the 25 patients. An association test showed that skin irritation was more frequent in patients who underwent allogeneic HSCT (p = 0.03). Skin irritation was most frequently observed in areas of contact with the non-woven polyester adhesive tape (n = 22;88%), which made up the adhesive margins of the dressing. The CIGD was discontinued in 6 (54%) of the 11 patients who presented severe skin injuries. Conclusion: In this study, we detected that skin irritation was more frequent in patients who underwent allogeneic HSCT. The most common skin manifestation was skin loss.

Low Dose Total Skin Electron Beam Radiation in Cutaneous T-Cell Lymphoma: Review

The treatment of advanced stage MF is especially challenging as single agent overall response rates are in the 35% range and chronic recurrence is the rule. The treatment of CTCL across all stages of disease is aimed at the goal of achieving and sustaining remission. Increasingly, low dose total skin electron beam therapy (TSEBT) is being utilized as a skin directed component in combination therapy for advanced stage CTCL. Researchers are seeking to better define the utility of low dose TSEBT as a method of debulking skin disease while simultaneously treating other disease compartments and in combination with sustained maintenance therapies of both the skin directed and systemic varieties. Data exists showing the efficacy of low dose TSEBT in early and advanced disease. There is also data documenting prolonged treatment responses with TSEBT plus adjuvant skin directed therapies such as PUVA and topical nitrogen mustard. Emerging data examining the role of low dose TSEBT in the prestem cell transplant preparation is also promising. This brief review summarizes the utility of low dose TSEBT in multiagent treatment regimens in CTCL.

Clinical Evaluation after Introduction of Stem Cell Supernatant Biocell Shot 65 by Electroporation

Objectives: The objective of this study is clinical evaluation after introduction of stem cell supernatant Biocell Shot 65 by electroporation. Background: There is a clinical report of psoriasis treatment by umbilical cord blood-derived stem cells, in which there was a beneficial result. These clinical results are the result of cord blood-derived cell growth factors. The umbilical cord blood-derived stem cell culture supernatant contains a high amount of TGF-β, PDGA, etc., and promotes wound healing. In addition, we suppose that the supernatant has the esthetic effect of improving skin condition, thus, we planned to make a clinical evaluation. However, it is difficult to set judgement criteria, and human judgement tends to be subjective. Therefore, in this study, as a new clinical evaluator, we used an AI skin diagnostic device with learning function. Methods: Stem cell culture supernatant Biocell Shot 65 was used as an introduction solution. After it was applied to the full faces of four patients, electroporation with BeBe pinocchio DM-5 SUPER DX Plus promoted infiltration deep in the keratinized layer. The patients were all healthy women in their forties. This procedure was performed every two weeks for three months. Wrinkles, fine lines around eyes, stains, pores, and 4V, which is considered as one diagnostic criteria, were evaluated at baseline and after each procedure with the skin diagnostic device HiMirror-Professional. In this study, macroscopic findings were not examined. Results: In all four patients, 4V did not change remarkably. Patient 1 showed improvement after the procedure in wrinkles, fine lines around eyes, stains, and pores. Patient 2 revealed improvement only in fine lines around eyes, but did not show improvement in other items. Patient 3 improved in wrinkles, stains, and pores only after the second procedure, but did not show improvement in the other procedures. Patient 4 improved in all items except 4V after the fourth procedure. In addition, when the mean values of all the patients were plotted and compared before and after each procedure, there was a trend toward improvements after the fifth procedure. Conclusion: In addition to application of supernatant culture to the skin, introduction of the solution to the skin by electroporation might improve stains, wrinkles, and pores. Our evaluation was performed with a facial diagnostic device three months after the start of the procedure.

母细胞性浆细胞样树突状细胞肿瘤临床和病理特征分析

目的:归纳并分析母细胞性浆细胞样树突状细胞肿瘤(BPDCN)的临床资料,为进一步认识该类疾病提供依据。方法:回顾性分析11例BPDCN患者的临床表现、免疫表型及病理特点、治疗与预后。结果:11例明确诊断BPDCN的患者中,男性8例、女性3例,中位年龄44(6-81)岁。临床主要以皮疹、包块等为首发症状,并伴有淋巴结、骨髓受累。肿瘤性母细胞性浆细胞样树突状细胞(pDC)表达HLA-DR、CD4、CD56、CD123,不表达cCD3、cMPO、cCD79a,部分病例可表达CD38、CD99、CD36。临床上手术切除、多次化疗失败的患者复发快,患者生存期短。首次化疗达到完全缓解的患者pDC细胞不表达CD56,且经骨髓移植后具有较长的生存期。结论:BPDCN免疫表型具有异质性,CD56是区分肿瘤性和正常pDC细胞的良好标志物;化疗缓解后进行造血干细胞移植的BPDCN患者预后较好。

提高间充质干细胞治疗皮瓣缺血再灌注损伤的策略

背景:间充质干细胞在治疗皮瓣缺血再灌注损伤方面潜力巨大,然而其自身的缺陷及在治疗皮瓣缺血再灌注损伤中的作用下降等原因限制了其广泛应用。目的:综述提高间充质干细胞治疗皮瓣缺血再灌注损伤的策略,为其进一步理论研究和临床应用提供参考。方法:检索中国知网、万方和PubMed数据库收录的相关文献。中文检索词为“间充质干细胞,皮瓣缺血再灌注损伤,间充质基质细胞,干细胞,皮瓣,缺血再灌注损伤,预处理,基因修饰,生物材料封装,联合运用”。英文检索词为“mesenchymal stem cell,Ischemia-reperfusion injury of skin flap,Mesenchymal stromal cells,Stem cells,skin flap,Ischemia-reperfusion injury,Pretreatment,Gene modification,Biomaterial packaging,Joint application”。检索2007年以来发表的相关文献,通过阅读文章剔除研究内容与文章主题关系不大、质量较差及内容陈旧的文献,最终纳入75篇文献进行归纳总结。结果与结论:①间充质干细胞具有抑制炎症反应、抗氧化应激以及诱导血管新生等显著作用,在治疗皮瓣缺血再灌注损伤中蕴含着巨大潜力。②尽管间充质干细胞在治疗皮瓣缺血再灌注损伤中显示出了巨大潜力,但其在治疗上存在的缺陷限制了在临床上的广泛运用,通过预处理(细胞因子、低氧、药物及其他预处理间充质干细胞)、基因修饰间充质干细胞、生物材料封装间充质干细胞以及间充质干细胞和其他药物或治疗方法联合运用等,这些方法不仅可以克服间充质干细胞在治疗上的缺陷,还提高了其在皮瓣缺血再灌注损伤方面的治疗效果。③因此,在未来进一步提高间充质干细胞治疗皮瓣缺血再灌注损伤的效果,挖掘其治疗潜力,对于间充质干细胞的研究和皮瓣缺血再灌注损伤的治疗都具有非常重要的意义。

模拟微重力环境对皮肤干细胞增殖影响的研究

目的研究皮肤干细胞在模拟微重力(SMG)环境下的增殖能力与干性变化。方法以SD大鼠皮肤干细胞为模型,建立悬浮培养体系,对比SMG环境与正常重力(1G)环境下皮肤干细胞的增殖及干细胞标志物的表达差异。结果SMG环境显著影响悬浮培养环境下的皮肤干细胞球增殖速度,其增殖率较1G重力组约高12%。转录组测序结果显示SMG组1673个基因上调,1409个基因下调;Calcium signaling、cytokine-cytokine receptor interaction及PPAR pathway等重要信号通路在两个环境下表达差异显著。结论SMG环境可通过调节关键信号通路的表达,影响悬浮培养环境下皮肤干细胞的增殖行为,为SMG环境下进一步研究工作提供了实验依据。

脂肪间充质干细胞负载生物打印支架对创面修复作用

目的 探讨壳聚糖基温敏水凝胶载体(4D-CTH)对脂肪间充质干细胞(ADSCs)的生物相容性以及对全层皮肤创面的修复作用。方法 采用酶消化法提取原代兔ADSCs,并应用流式细胞术和多向分化实验对其进行鉴定。体外共培养4D-CTH和ADSCs,分别采用活/死细胞染色、CCK-8以及荧光划痕方法测定4D-CTH的生物相容性。构建皮肤全层缺损模型,随机将兔分为Control组(用100μL PBS缓冲液对创面进行处理)、ADSCs组(用100μL ADSCs悬液对创面进行处理)以及4D-CTH+ADSCs组(应用4D-CTH转载ADSCs对创面进行处理)。在治疗14 d后,拍照观察各组创面愈合率。结果 提取的兔ADSCs呈长梭形,其表面标记分子CD44、CD90呈阳性表达,内皮细胞标记物CD45以及巨噬细胞标记物CD11b呈阴性表达,ADSCs具备多向分化潜力。活/死细胞染色结果显示,组别、时间、组别和时间的交互效应对细胞活力无影响(F_(组别)=0.716,P>0.05;F_(时间)=1.219,P>0.05;F_(组别×时间)=1.567,P>0.05)。CCK-8检测结果显示,组别、组别和时间的交互效应对细胞增殖率无影响(F_(组别)=1.995,P>0.05;F_(组别×时间)=0.321,P>0.05),不同时间点细胞增殖率差异有统计学意义(F_(时间)=1 408.000,P<0.01)。荧光划痕实验结果显示,组别、组别和时间的交互效应对细胞迁移率无影响(F_(组别)=2.184,P>0.05;F_(组别×时间)=0.108,P>0.05),不同时间点细胞迁移率差异有统计学意义(F_(时间)=50.110,P<0.01)。创面愈合实验结果显示,各组创面愈合率差异有显著意义(F=9.778~49.910,P<0.01),4D-CTH+ADSCs组创面愈合率最高。结论 4D-CTH转载ADSCs可以加速皮肤创面愈合,促进皮肤再生。

脂肪间充质干细胞对巴马小型猪自体皮肤移植愈合过程的影响

拟应用脂肪间充质干细胞(adipose derived mesenchymal stem cells,ADSCs)干预小型猪自体皮肤移植实验动物模型,观察其对自体皮肤移植愈合过程中的作用效果。对9头小型猪建立自体皮肤移植动物模型,将小型猪随机分为3组:模型组(Model)、磷酸盐缓冲液组(PBS)、脂肪间充质干细胞组(ADSCs)。各组分别于术前,术后7、14、21和28 d,采集血液和皮肤组织样本,并观察、拍照、记录移植皮片和周围组织临床变化情况。通过对移植皮片表观检查、病理组织学检测,血常规以及血清生化检测,移植皮片组织氧化应激、炎症、再生相关指标检测及血流恢复情况,综合评价ADSCs对小型猪自体皮肤移植创口愈合的影响。临床观察发现,术后ADSCs组皮片恢复速度优于其他两组,在术后28 d,ADSCs组基本恢复正常皮肤状态。在氧化应激方面,ADSCs组SOD、GSH含量显著升高(0.01<P<0.05),MDA显著下降(0.01<P<0.05)。在炎症方面,ADSCs组显著降低TNF-α、IL-1β含量,IL-10在术后7、14 d极显著升高(P<0.01)。在皮肤组织再生方面,ADSCs组VEGF、bFGF、TGFβ3和CD31的表达量显著上升(0.01<P<0.05)。在血流恢复方面,ADSCs在愈合过程中血流灌注百分比显著高于其他两组(0.01<P<0.05)。综上表明,在小型猪自体皮肤移植动物模型中,ADSCs能够加速皮肤组织病理损伤的恢复,降低氧化应激反应及炎症反应,促进皮肤组织再生,血管新生。表明ADSCs具有抗氧化、抗炎和促进组织再生的功能对小型猪自体皮肤移植具有良好的治疗效果,本试验为干细胞在自体皮肤移植和异体皮肤移植的临床应用提供了实验支撑和科学依据。

免疫缺陷儿童诺卡菌病后造血干细胞移植一例并文献复习

诺卡氏菌病是一种人畜共患病,机会性侵入机体后引起不同程度的人畜疾病,免疫抑制或缺陷个体易感,缺乏临床特异性表现的罕见病。近年来,病例报道明显增加,本文阐述儿童诺卡菌肺部及皮肤感染治愈后进行造血干细胞移植术1例,回顾诺卡氏菌的概述、感染途径及致病性、诊断及治疗等进行综述。

丙二醇联合肝细胞生长因子修饰牙髓干细胞外泌体保护人表皮细胞的放射损伤

背景:肿瘤放疗以及核事故等原因引起的放射性皮肤损伤救治仍旧是一个严重的医学问题,单一的防治手段均难以达到有效的治疗结果,寻找新的综合治疗手段是重要的研究方向。目的:观察丙二醇联合肝细胞生长因子修饰牙髓干细胞来源外泌体对于人表皮放射性损伤细胞模型的保护作用及相关作用机制。方法:①使用携带人肝细胞生长因子基因的重组腺病毒感染人牙髓干细胞,超速离心法分离制备外泌体,即Ad.HGF DPSC-Exo。②通过X射线照射诱导人表皮细胞HaCaT放射损伤,细胞分别于照射前用丙二醇预处理,照射后用Ad.HGF DPSC-Exo处理。通过CCK-8法测定细胞增殖活力,流式细胞术检测细胞凋亡情况,细胞划痕实验检测细胞迁移情况,PCR检测P21和P53的表达水平。结果与结论:丙二醇、Ad.HGF.DPSC-Exo、Ad.HGF.DPSC-Exo+丙二醇均可显著改善HaCaT细胞的生长抑制、减少细胞凋亡、提高细胞增殖和迁移能力,显示出较好的辐射防护效果,且Ad.HGF.DPSC-Exo+丙二醇联合作用效果更好。此外,Ad.HGF.DPSC-Exo+丙二醇能够减轻细胞G2/M期阻滞,降低细胞周期调控基因P53和P21的表达。综上所述,丙二醇预处理联合Ad.HGF.DPSC-Exo能够有效保护放射诱导的HaCaT细胞损伤,为辐射性皮肤损伤的防治提供了新的思路和有效方法。