scholarly journals Design of In Vitro Hair Follicles for Different Applications in the Treatment of Alopecia—A Review

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 435
Author(s):  
Matej Žnidarič ◽  
Žan Michel Žurga ◽  
Uroš Maver

The hair research field has seen great improvement in recent decades, with in vitro hair follicle (HF) models being extensively developed. However, due to the cellular complexity and number of various molecular interactions that must be coordinated, a fully functional in vitro model of HFs remains elusive. The most common bioengineering approach to grow HFs in vitro is to manipulate their features on cellular and molecular levels, with dermal papilla cells being the main focus. In this study, we focus on providing a better understanding of HFs in general and how they behave in vitro. The first part of the review presents skin morphology with an emphasis on HFs and hair loss. The remainder of the paper evaluates cells, materials, and methods of in vitro growth of HFs. Lastly, in vitro models and assays for evaluating the effects of active compounds on alopecia and hair growth are presented, with the final emphasis on applications of in vitro HFs in hair transplantation. Since the growth of in vitro HFs is a complicated procedure, there is still a great number of unanswered questions aimed at understanding the long-term cycling of HFs without losing inductivity. Incorporating other regions of HFs that lead to the successful formation of different hair classes remains a difficult challenge.

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 110-115 ◽  
Author(s):  
Susan Yung ◽  
Chan Tak Mao

♦ Background The introduction of peritoneal dialysis (PD) as a modality of renal replacement therapy has provoked much interest in the biology of the peritoneal mesothelial cell. Mesothelial cells isolated from omental tissue have immunohistochemical markers that are identical to those of mesothelial stem cells, and omental mesothelial cells can be cultivated in vitro to study changes to their biologic functions in the setting of PD. ♦ Method The present article describes the structure and function of mesothelial cells in the normal peritoneum and details the morphologic changes that occur after the introduction of PD. Furthermore, this article reviews the literature of mesothelial cell culture and the limitations of in vitro studies. ♦ Results The mesothelium is now considered to be a dynamic membrane that plays a pivotal role in the homeostasis of the peritoneal cavity, contributing to the control of fluid and solute transport, inflammation, and wound healing. These functional properties of the mesothelium are compromised in the setting of PD. Cultures of peritoneal mesothelial cells from omental tissue provide a relevant in vitro model that allows researchers to assess specific molecular pathways of disease in a distinct population of cells. Structural and functional attributes of mesothelial cells are discussed in relation to long-term culture, proliferation potential, age of tissue donor, use of human or animal in vitro models, and how the foregoing factors may influence in vitro data. ♦ Conclusions The ability to propagate mesothelial cells in culture has resulted, over the past two decades, in an explosion of mesothelial cell research pertaining to PD and peritoneal disorders. Independent researchers have highlighted the potential use of mesothelial cells as targets for gene therapy or transplantation in the search to provide therapeutic strategies for the preservation of the mesothelium during chemical or bacterial injury.


1991 ◽  
Vol 99 (3) ◽  
pp. 627-636 ◽  
Author(s):  
C.A. Jahoda ◽  
A.J. Reynolds ◽  
C. Chaponnier ◽  
J.C. Forester ◽  
G. Gabbiani

We have examined the expression of smooth muscle alpha-actin in hair follicles in situ, and in hair follicle dermal cells in culture by means of immunohistochemistry. Smooth muscle alpha-actin was present in the dermal sheath component of rat vibrissa, rat pelage and human follicles. Dermal papilla cells within all types of follicles did not express the antigen. However, in culture a large percentage of both hair dermal papilla and dermal sheath cells were stained by this antibody. The same cells were negative when tested with an antibody to desmin. Overall, explant-derived skin fibroblasts had relatively low numbers of positively marked cells, but those from skin regions of high hair-follicle density displayed more smooth muscle alpha-actin expression than fibroblasts from areas with fewer follicles. 2-D SDS-PAGE confirmed that, unlike fibroblasts, cultured papilla cells contained significant quantities of the alpha-actin isoform. The rapid switching on of smooth muscle alpha-actin expression by dermal papilla cells in early culture, contrasts with the behaviour of smooth muscle cells in vitro, and has implications for control of expression of the antigen in normal adult systems. The very high percentage of positively marked cultured papilla and sheath cells also provides a novel marker of cells from follicle dermis, and reinforces the idea that they represent a specialized cell population, contributing to the heterogeneity of fibroblast cell types in the skin dermis, and possibly acting as a source of myofibroblasts during wound healing.


2020 ◽  
Vol 21 (14) ◽  
pp. 5137
Author(s):  
Jung Eun Kim ◽  
Yu Jin Lee ◽  
Hye Ree Park ◽  
Dong Geon Lee ◽  
Kwan Ho Jeong ◽  
...  

Topical or systemic administration of JAK inhibitors has been shown to be a new treatment modality for severe alopecia areata (AA). Some patients show a good response to JAK inhibitors, but frequently relapse after cessation of the treatment. There have been no guidelines about the indications and use of JAK inhibitors in treating AA. The basic pathomechanism of AA and the relevant role of JAK inhibitors should support how to efficiently use JAK inhibitors. We sought to investigate the effect of JAK1/2 inhibitor on an in vitro model of AA and to examine the possible mechanisms. We used interferon gamma-pretreated human dermal papilla cells (hDPCs) as an in vitro model of AA. Ruxolitinib was administered to the hDPCs, and cell viability was assessed. The change of expression of the Wnt/β-catenin pathway, molecules related to the JAK-STAT pathway, and growth factors in ruxolitinib-treated hDPCs was also examined by reverse transcription PCR and Western blot assay. We examined immune-privilege-related molecules by immunohistochemistry in hair-follicle culture models. Ruxolitinib did not affect the cell viability of the hDPCs. Ruxolitinib activated several molecules in the Wnt/β-catenin signaling pathway, including Lef1 and β-catenin, and suppressed the transcription of DKK1 in hDPCs, but not its translation. Ruxolitinib reverted IFN-γ-induced expression of caspase-1, IL-1β, IL-15, and IL-18, and stimulated several growth factors, such as FGF7. Ruxolitinib suppressed the phosphorylation of JAK1, JAK2 and JAK3, and STAT1 and 3 compared to IFN-γ pretreated hDPCs. Ruxolitinib pretreatment showed a protective effect on IFN-γ-induced expression of MHC-class II molecules in cultured hair follicles. In conclusion, ruxolitinib modulated and reverted the interferon-induced inflammatory changes by blocking the JAK-STAT pathway in hDPCs under an AA-like environment. Ruxolitinib directly stimulated anagen-re-entry signals in hDPCs by affecting the Wnt/β-catenin pathway and promoting growth factors in hDPCs. Ruxolitinib treatment prevented IFN-γ-induced collapse of hair-follicle immune privilege.


2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Zhenyu Wu ◽  
Yanli Zhu ◽  
Hongli Liu ◽  
Gongyan Liu ◽  
Fuchang Li

Abstract Wnt signaling plays an important role in the growth and development of hair follicles (HFs). Among the signaling molecules, Wnt10b was shown to promote the differentiation of primary skin epithelial cells toward the hair shaft and inner root sheath of the HF cells in mice in vitro. Whisker HFs were isolated from Rex rabbits and cultured in vitro to measure hair shaft growth. Meanwhile, dermal papilla cells (DPCs) were isolated and cultured in vitro. Treatment with AdWnt10b or the Wnt/β-Catenin Pathway inhibitor, XAV939, assessed the DPCs proliferation by CCK-8 assay. And the cell cycle was also analyzed by flow cytometry. We found that Wnt10b could promote elongation of the hair shaft, whereas XAV-939 treatment could eliminated this phenomenon. AdWnt10b treatment promoted the proliferation and induced G1/S transition of DPCs. AdWnt10b stimulation up-regulated β-Catenin protein in DPCs. Inhibition of Wnt/β-Catenin signaling by XAV-939 could decreased the basal and Wnt10b-enhanced proliferation of DPCs. And could also suppress the cell cycle progression in DPCs. In summary, our study demonstrates that Wnt10b could promote HFs growth and proliferation of DPCs via the Wnt/β-Catenin signaling pathway in Rex rabbits.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jae Young Yu ◽  
Biki Gupta ◽  
Hyoung Geun Park ◽  
Miwon Son ◽  
Joon-Ho Jun ◽  
...  

The proprietary DA-5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA-5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA-5512. DA-5512 significantly enhanced the viability of hDPCs in a dose-dependent manner (p<0.05), and 100 ppm of DA-5512 and 1 μM minoxidil (MXD) significantly increased the number of Ki-67-positive cells, compared with the control group (p<0.05). MXD (3%) and DA-5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p<0.05). The groups treated with DA-5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA-5512 after 16 weeks compared with the groups treated with placebo or 3% MXD (p<0.05). In conclusion, DA-5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tatsuto Kageyama ◽  
Yang-Sook Chun ◽  
Junji Fukuda

AbstractHair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss. Recent advances in three-dimensional tissue engineering, such as formation of hair follicle germs (HFGs), have considerably improved hair regeneration after transplantation in animal models. Here, we proposed an approach for fabricating HFGs containing vascular endothelial cells. Epithelial, dermal papilla, and vascular endothelial cells initially formed a single aggregate, which subsequently became a dumbbell-shaped HFG, wherein the vascular endothelial cells localized in the region of dermal papilla cells. The HFGs containing vascular endothelial cells exhibited higher expression of hair morphogenesis-related genes in vitro, along with higher levels of hair shaft regeneration upon transplantation to the dorsal side of nude mice, than those without vascular endothelial cells. The generated hair follicles represented functional characteristics, such as piloerection, as well as morphological characteristics comparable to those of natural hair shafts. This approach may provide a promising strategy for fabricating tissue grafts with higher hair inductivity for hair regenerative medicine.


Development ◽  
1984 ◽  
Vol 79 (1) ◽  
pp. 211-224
Author(s):  
Colin A. B. Jahoda ◽  
Roy F. Oliver

Parallel cultures of adult rat vibrissa dermal papilla cells and skin fibroblasts revealed differences between the two cell types with respect to a number of criteria. In particular the dermal papilla cells demonstrated a distinctive single cell morphology, and at confluence formed cell aggregates radically different from regular fibroblast multilayering and patterning. This finding confirmed repeated observations of papilla cell clumping in short-term culture. The dermal papilla cells which are mitotically quiescent in situ were also shown to have a lower proliferative capacity than the skin fibroblasts. The affinity shown by papilla cells towards each other in culture reflected the behaviour demonstrated by isolated dermal papillae transplanted into ear dermis and into the collagenous capsule of the vibrissa follicle. In the absence of epidermal contact the papilla cells remained as recognizable rounded aggregates for the experimental period of up to nine months. Synthesis of extracellular material typical of that seen in situ was observed, particularly during the first weeks following transplantation. The collective behaviour of the dermal papilla cells revealed in this study may be significant for the morphogenetic activity of the papilla, and for papilla size during the hair cycle. It may also reflect the retention of embryonic-like properties by the dermal component of adult hair follicles.


Author(s):  
Christopher I. Platt ◽  
Jeremy Chéret ◽  
Ralf Paus

AbstractOrgan culture of microdissected scalp hair follicles (HFs) has become the gold standard for human ex vivo hair research; however, availability is becoming very limited. Although various simplistic “HF-equivalent” in vitro models have been developed to overcome this limitation, they often fail to sufficiently mimic the complex cell–cell and cell–matrix interactions between epithelial and mesenchymal cell populations that underlie the specific growth processes occurring in a native HF. Here, we have attempted to overcome these limitations by developing a novel human hair research model that combines dermal papilla (DP) fibroblasts, cultured as 3-dimensional (3D) spheroids (DPS), with plucked anagen hair shafts (HS). We show that DPS express HF inductivity markers, such as alkaline phosphatase (ALP), versican and noggin, while plucked HSs retain substantial remnants of the anagen hair matrix. When cultured together, DPS adhere to and surround the plucked HS (HS-DPS), and significantly enhance HS expression of the differentiation marker keratin-85 (K85; p < 0.0001), while simultaneously decreasing the percentage of TUNEL + cells in the proximal HS (p = 0.0508). This simple model may offer a physiologically relevant first step toward evaluating HF differentiation in the human anagen hair matrix.


2021 ◽  
Vol 11 (20) ◽  
pp. 9485
Author(s):  
Paolo Raffa ◽  
Maria Easler ◽  
Francesca Cecchinato ◽  
Beatrice Auletta ◽  
Valentina Scattolini ◽  
...  

Decellularized skeletal muscle (dSkM) constructs have received much attention in recent years due to the versatility of their applications in vitro. In search of adequate in vitro models of the skeletal muscle tissue, the dSkM offers great advantages in terms of the preservation of native-tissue complexity, including three-dimensional organization, the presence of residual signaling molecules within the construct, and their myogenic and neurotrophic abilities. Here, we attempted to develop a 3D model of neuromuscular tissue. To do so, we repopulated rat dSkM with human primary myogenic cells along with murine fibroblasts and we coupled them with organotypic rat spinal cord samples. Such culture conditions not only maintained multiple cell type viability in a long-term experimental setup, but also resulted in functionally active construct capable of contraction. In addition, we have developed a customized culture system which enabled easy access, imaging, and analysis of in vitro engineered co-cultures. This work demonstrates the ability of dSkM to support the development of a contractile 3D in vitro model of neuromuscular tissue fit for long-term experimental evaluations.


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