外文文献翻译

Cell-Type-Specific Differentiation andMolecular Profiles

in Skin Transplantation: Implication ofMedical Approach

for Genetic Skin Diseases

1.Introduction 前言

In skin transplantation biology, multistage and multifocal damages occur in both grafted donor and perilesional host skin and need to be repaired properly for the engraftment and maintenance of characteristic skin architecture.

在皮肤移植生物学中，多级和多焦损害发生在嫁接的捐助和高血压宿主皮肤和需要妥善修复植入和维护皮肤典型体系结构。

These local events are more unlikely to be regulated by the host immunity, because human skin transplantation has accomplished the donor skin engraftment onto the immunocompromised or immunosuppressive animals. Recent

这些地方的事件是受宿主免疫，更可能的因为人体皮肤移植取得捐助者皮肤植入到免疫缺陷或免疫抑制剂动物。

From a dermatological viewpoint, we review the recent update of cell-type- and molecular-specific action associated with reconstitution of the grafted skin and also focus on the novel application of BM transplantation medicine in genetic skin diseases.

从皮肤病学的角度来看，我们审查与移植的皮肤重建相关联的特定细胞类型和分子操作新的更新，也侧重于BM 移植医学在遗传皮肤疾病中应用。Pathologically, the predominant cell populations in mammalian skin comprise dermal fibroblasts and epidermal keratinocytes, both of which show different morphology and Function

哺乳动物的皮肤包括真皮成纤维细胞及表皮角质形成细胞，这两个细胞表明不同的形态和功能。

Upon these in vitro skin equivalent assays, our potential interests persist to know how these two cell types are reorganised properly in the grafted skin

对这些在体外皮肤等效试验，我们潜在的兴趣坚持想知道这些类型的两个细胞，如何会在适当的进行重组移植的皮肤。

At the site of the skin graft, multistage and multifocal damages of the donor/host skin, microhaemorrhage,and later excess fibrosis in the dermis might have eventually occurred, and the grafted skin, therefore, needs to be repaired and reconstituted through these inevitable events.

在皮肤移植中，多级和多焦捐助者/主机皮肤的损伤，而后来过剩纤维和移植的皮肤在真皮层可能最终发生，因此，需要修理和重组通过这些不可避免的事件。

More specifically, little is known about how the biological architecture characteristic for the skin (e.g., stratified squamoid epithelia and dermis intermixed with extracellular matrices) can be maintained after the skin transplantation.

而且，对如何生物体系结构（例如，分层脂性皮肤特性上皮细胞和真皮层混杂与胞外基质）可以保持皮肤移植术后知之甚少。

One may consider that a sort of particular cell phenotypes plays a central role in the orchestration of the skin reconstitution,and, if so, under what particular circumstances for this process? The chain of these biological events is more unlikely to be regulated by cellular and humoral immunity in the host, because vast majority of in vivo researches for human skin transplantation has accomplished the donor skin engraftment onto the immunocompromised animals,such as nude and athymic mice, or those treated with immunosuppressive agents or the particular subset (CD4+ CD25+) of T cells . Thus, a somewhat study limitation may often enable us to access to the insight associated with the skin transplantation immunobiology.

一个人可以考虑一种特定的细胞表型在皮肤重建，业务流程中的核心作用，如果是这样，在特定情况下为此过程吗？这些生物事件链是更不太可能应由细胞和体液免疫的影响主机，因为绝大多数的体内研究人体皮肤移植取得捐助者皮肤移植到免疫功能低下的动物身上，如裸照和裸鼠的小鼠，或那些处理免疫抑制剂或特定的子集（CD4 + CD25+）的 T 细胞。因此，某种程度上的研究限制

可能经常使我们能够访问到洞察与关联皮肤移植免疫。

For understanding the cell-specific action in the skin transplantation, evidences from bone marrow (BM) transplantation study may in part bring the clue.

为了解在皮肤的细胞特定的操作移植，来自骨髓（BM）移植的证据研究部分可能带来线索。

Native BM cells comprise the substantial proportion of cell sources that have roles in tissue homeostasis, repair, and regeneration.

本机的骨髓细胞包括相当比例的有的细胞在组织的平衡、修复和再生中发挥作用。

These cell populations are originated fromeither haematopoietic or mesenchymal stem cells and subpopulations that are capable

of differentiating into multiple cell lineages .

这些细胞群是起源于造血或骨髓间充质干细胞和有能力的亚群

分化为多种细胞谱系。

A series of recent research progress have emerged that BM cells can provide not only fibroblastic cells but also epithelial cells in the lung and intestinal epithelium and skin .

一系列最近的研究进展出现了 BM 细胞可以提供不仅是成纤维细胞, 还包括肺

上皮细胞、肠上皮细胞和皮肤。

Particularly in skin, a transplantation of sex (XY) chromosomemi smatched BM cells or intrinsically labelled BM cells has demonstrated that keratinocyte-specific marker-positive BM cells appeared in the epidermis, hair follicles and sebaceous glands .

特别是在皮肤移植中，骨髓细胞或本质上标记的骨髓细胞已表明，角质形成细胞特异性标志物阳性 BM细胞出现在表皮，毛囊和皮脂腺腺体。

Moreover, in patients who underwent a BM transplantation, donor BM cells displaying wideranged keratinocyte markers (pan-keratin) were detectable in the epidermis and maintained for over 3 years after the transplantation .

此外，在患者骨髓移植中，捐助骨髓细胞显示角质形成细胞标记（潘角蛋白）中被检出在表皮移植后维持三年以上。

These data series suggest that the transdifferentiated keratinocytes from BM cells not only aid the impairment of the residual epidermal function after transplantation but also participate in the compensation of the epidermal circumstances at the affected skin sites.

这些数据系列表明角质形成细胞从骨髓细胞不仅是援助移植术后残留表皮的功

能障碍但也参与了补偿受感染的皮肤部位表皮的情况。

On this basis, the BM-derived keratinocyte populations are secured functionally and structurally as a baseline stable supply.

在此基础上BM 派生的角质形成细胞群体作为一个基线稳定供应担保功能和结构。

However, it remains unclear how the BM cells are

recruited strictly into the grafted skin, and, if once they failed

this process, how it can be corrected properly, (ii) how the

recruited BM cells contribute functionally to the local skin regeneration, and, more interestingly, (iii) whether the newly established epithelial-mesenchymal interaction can maintain

the local skin homeostasis analogous to the host skin.

然而，尚不清楚骨髓细胞怎样严格招入的移植的皮肤，如果一旦他们失败，这一进程，它如何正确纠正，如何植入的骨髓细胞功能有助于局部皮肤再生，更有趣的是，是否新建立上皮-间充质细胞相互作用可以维持局部皮肤稳态类似于宿主皮肤。

From a dermatological view point, this paper focuses mainly on

these attractive points in association with the cell-typespecific reorganization in the skin transplantation, as well

as the relevant molecular profiles.

从皮肤病学的观点来看，本文主要对这些有吸引力的细胞具有型特异性结合点

在皮肤移植中的重组作为相关的分子配置文件。

These advanced evidences will help to ask how we can establish the better medical approaches for persistent skin wound condition, particularly in genetic skin diseases.

这些先进的证据将有助于问我们如何可以建立更佳的医疗方法对于持续皮肤伤口条件，特别是在遗传皮肤疾病。

2.Myofibroblasts in Skin Transplantation:What It Is, How It Acts, and Where It Comes from?

肌成纤维细胞在皮肤移植：它是什么，它如何让工作，它来自的何地？

After skin transplantation, the grafted skin sites need to repair some inevitable minor trauma, for example, occasional haemorrhage caused by microvascular damage, later excess microfibrosis, or even focal necrotic changes, in order to adapt to the host skin circumstance.

皮肤移植术后，移植的皮肤站点需要修复一些必然轻微外伤，例如，偶尔出血后引起的微血管损害，多余的纤维或甚至局灶性坏死变化，为适应宿主的皮肤情况。These minor tissue damages in the grafted donor skin and/or perilesional host skin may primarily drive the recruitment of the particular subset of fibroblastic cells, termed “myofibroblasts” that specifically express the intracellular structural protein α-smooth muscle actin (α-SMA) .

这些微小的组织嫁接的捐助者的皮肤和高血压宿主中的损害赔偿皮肤可能主要驱动特殊性的植入的成纤维细胞的细胞，被称为"肌成纤维细胞"，具体表达细胞结构蛋白α-平滑肌肌动蛋白（α-SMA）。

Myofibroblasts can migrate into the grafted skin and subsequently produce collagens, fibronectin, and proteoglycans to reconstitute the local extracellular matrix (ECM) network in the dermis.

肌成纤维细胞可以迁移到移植的皮肤和随后产生胶原蛋白、纤维连接蛋白和蛋白多糖来重建在真皮层的局部细胞外基质（ECM）网络。

During this process, α-SMA is reorganised into the complexes of stress fibre for biological connecting to the surrounding ECM molecules and participates in the exert contraction and mechanical tension, as well as reconstitution of primary intra-/intercellular skeleton, for the establishment of the functional remodelling of connective tissue.

在此过程中，α-SMA 被重组为配合物应力纤维的生物连接到周围的 ECM 分子和参与发挥收缩和机械的张力，以及重组主内的细胞骨架，为建立的结缔组织功能重塑组织。

In contrast, persistence and/or aberrant increase of myofibroblast action may be responsible for fibrosclerotic skin diseases, such as scleroderma or morphea .

在对比中，持久性和/或异常的增加肌成纤维细胞行动可能会导致胶原纤维皮肤疾病，如硬皮病或局限性。

Another in vitro observation with human embryonic stem (hES) cells utilizing a three-dimensional skin model has shown that hES cell-derived mesenchymal cells that constitutively express α-SMA can promote multilayered epithelium and the resultant wound healing, with increased production of hepatocyte growth factor HGF, an essential factor for skin development and repair .

另一种人类胚胎干（hES）细胞的体外观察，利用一个三维的皮肤模型表明，人类胚胎干细胞源性间充质细胞组成性表达的α-SMA 可以促进多层上皮细胞和由此产生的伤口愈合，增加生产的肝细胞生长因子，肝细胞生长因子促进皮肤发育的基本因素和修复。

This characteristic cell phenotype might also be analogous to myofibroblastic cell lineage, with possible implication of

epidermal-mesenchymal crosstalk in a HGF-dependent manner.

此特性的细胞表型可能也是类似于肌纤维母细胞细胞谱系，与肝细胞生长因子依赖性的表皮间充质串扰的可能意义。

The local myofibroblasts—without regard to the newly recruited into the donor grafted skin or locally residential cells—are considered to be originated from multiple cell sources in vivo.

当地肌成纤维细胞—不顾新植入嫁接皮肤或本地原来细胞—被认为起源于多个体内的细胞来源

Current concept favours at least 3 distinct cell sources of skin myofibroblasts (Figure 1): (i) pericytes that composed of skin microvasculature, (ii) resident fibroblasts in the donor grafted skin and/or in the perilesional host skin, or (iii) BM-derived mesenchymal stem cells .

当前概念认为至少3个不同细胞来源的皮肤肌成纤维细胞：(i) 周细胞，组成皮肤微血管，(ii) 驻地成纤维细胞组成捐助者嫁接皮肤和（或）高血压主机皮肤或者 (iii) BM-间充质干细胞。

These myofibroblast sources may be selective and changeable appropriately in a skin-damage-dependent manner .

这些肌成纤维细胞来源可能是选择性和适当地在皮肤损伤的依赖性多变However, there have been no convincing data for what percentage of the particular cell-lineage-derived myofibroblasts is involved in the reconstitution of the skin graft.

然而，有多少百分比的特定细胞源性沿袭肌成纤维细胞参与重建的皮肤移植没有令人信服的数据。

Also, little is known about whether any biological thresholds of the myofibroblast recruitment exist in this event.

此外，很少有人知道是否任何生物的阈值肌成纤维细胞植入在此事件中存在。

Noritaka oyama ,Fumio kaneko ,Matthew Griffin.

Cell-Type-Specific Differentiation and Molecular Profiles in Skin Transplantation: Implication of Medical Approach for Genetic Skin Diseases.

Journal of Transplantation, 2011, Vol.2011