Blank Spots in the Map of Human Skin: The Challenge for Xenotransplantation

August 2023 in “ International Journal of Molecular Sciences ”

Olga L. Cherkashina, E. I. Morgun, A. Rippa, A. V. Kosykh, А. В. Алехнович, Aleksey B. Stoliarzh, V. V. Terskikh, E. A. Vorotelyak, Ekaterina P. Kalabusheva

Studysummary This review discusses the use of human-to-mouse xenografting to study human skin processes in vivo, highlighting its importance for understanding skin regeneration and pathology while identifying knowledge gaps and challenges in applying these findings to human skin.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

The review "Blank Spots in the Map of Human Skin: The Challenge for Xenotransplantation" discusses the limitations and potential of xenotransplantation, specifically human-to-mouse, in studying human skin. The study of human skin is restricted due to factors such as genetic, age, and individual differences between donors, and the inability to trace changes over time. Xenotransplantation of human skin into laboratory animals, a practice that has evolved over the past 50 years, offers a way to study human skin in a more controlled and replicable manner. The document also discusses the structure and function of the human skin, focusing on the epidermis, dermis, hair follicles, and wound healing. It highlights the role of dermal fibroblasts, particularly Engrailed 1 (En1)/CD26-positive cells, in wound healing and fibrosis progression. The elimination of these fibroblasts resulted in no scarring and significant hair growth by 30 days. The document concludes by highlighting the potential of human skin xenografting combined with a single cell approach to advance our understanding of human skin development, self-renewal, and regeneration.

View this study on mdpi.com →

Discuss this study in the Community →

Research cited in this study

34 / 34 results

research A Kaleidoscope of Keratin Gene Expression and the Mosaic of Its Regulatory Mechanisms

3 citations , March 2023 in “International journal of molecular sciences”

This review discusses the patterns and regulatory mechanisms of keratin expression in various biological conditions and reports no new experimental results.

research Involvement of ILC1-Like Innate Lymphocytes in Human Autoimmunity: Lessons from Alopecia Areata

18 citations , February 2023 in “eLife”

This study indicates that innate lymphoid cells-type 1 may provoke alopecia areata by disrupting hair follicle immune privilege and inducing characteristic lesions, challenging the view that alopecia areata is purely an autoantigen-dependent, T cell-driven condition.

research Wound-Induced Hair Neogenesis Model

5 citations , September 2022 in “Journal of Investigative Dermatology”

This review discusses factors affecting wound-induced hair neogenesis in mice and reports no new results; it aims to facilitate meaningful comparisons of experiments across different laboratories.

research Morphogenesis, Growth Cycle, and Molecular Regulation of Hair Follicles

21 citations , May 2022 in “Frontiers in Cell and Developmental Biology”

This review covers the structure, development, cycle, and molecular regulation of hair follicles but does not report new results, aiming to offer insights for addressing hair follicle-related diseases.

research The Influence of CD26+ and CD26− Fibroblasts on the Regeneration of Human Dermo-Epidermal Skin Substitutes

11 citations , February 2022 in “Scientific Reports”

This study found that CD26+ fibroblasts are crucial for effective extracellular matrix production and achieving rapid epidermal and dermal homeostasis in human tissue-engineered skin substitutes transplanted onto rodents.

research Emerging Role of Dermal White Adipose Tissue in Modulating Hair Follicle Development During Aging

5 citations , October 2021 in “Frontiers in Cell and Developmental Biology”

This study examined aging hair follicle stem cells in mice and found that inflammation reduction in dermal white adipose tissue can stimulate regenerative behavior, highlighting its role in hair follicle aging.

research Dermal Adipose Tissue Secretes HGF to Promote Human Hair Growth and Pigmentation

29 citations , January 2021 in “Journal of Investigative Dermatology”

This study demonstrates that dermal white adipose tissue regulates human hair growth and pigmentation through hepatocyte growth factor secretion, highlighting potential therapeutic targets for hair-related disorders.

research Epidermal Stem Cells in Hair Follicle Cycling and Skin Regeneration: A View From the Perspective of Inflammation

18 citations , November 2020 in “Frontiers in Cell and Developmental Biology”

This review discusses how inflammation influences hair follicle stem cell activities like wound healing and follicle cycling and suggests a potential link between inflammation, stem cell activation, and programmed cell death.

research Distinct Regulatory Programs Control the Latent Regenerative Potential of Dermal Fibroblasts During Wound Healing

128 citations , August 2020 in “Cell stem cell”

In this study, researchers found that extrafollicular progenitors marked by Hic1 are the main contributors to reparative fibroblasts in wound repair, with potential to modulate healing outcomes through genetic and pharmacological interventions.

research Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair

124 citations , June 2020 in “Cell Stem Cell”

This study found that in mice, dermal adipocytes initiate inflammation and aid repair after skin injury by releasing lipids, suggesting a role in managing inflammatory diseases and impaired wound healing.

research Immune Modulation of Hair Follicle Regeneration

29 citations , May 2020 in “npj Regenerative Medicine”

This review discusses the role of the immune niche in hair follicle regeneration and its impact on different forms of alopecia, highlighting research gaps and potential therapeutic strategies.

research Functional Complexity of Hair Follicle Stem Cell Niche and Therapeutic Targeting of Niche Dysfunction for Hair Regeneration

59 citations , March 2020 in “Journal of Biomedical Science”

This study explored the complex roles of niche cells in regulating hair follicle stem cells, identifying specific cell functions such as signaling, sensing, and relaying messages, which could provide insights into treating hair loss conditions like androgenetic alopecia and alopecia areata.

research Dermal Adipose Tissue Has High Plasticity And Undergoes Reversible Dedifferentiation In Mice

136 citations , September 2019 in “Journal of Clinical Investigation”

This study found that mature dermal adipocytes have high plasticity, undergoing dedifferentiation and redifferentiation, which plays a significant role in hair cycling and wound healing.

research Regeneration of Dermis: Scarring and Cells Involved

176 citations , June 2019 in “Cells”

This review discusses dermal cell heterogeneity in wound healing and scar formation, highlighting the varied roles of different fibroblasts and the potential of skin substitutes without presenting new clinical results.

research Single-Cell Transcriptomics of Traced Epidermal and Hair Follicle Stem Cells Reveals Rapid Adaptations During Wound Healing

209 citations , October 2018 in “Cell Reports”

This study found that Lgr5 and Lgr6 stem cells both activated wound-healing genes, but only Lgr5 stem cells changed their identity to contribute to new skin formation during wound repair.

research iNKT Cells Ameliorate Human Autoimmunity: Lessons from Alopecia Areata

27 citations , April 2018 in “Journal of autoimmunity”

In this study, iNKT10 cells were found to play a significant role in preventing and treating alopecia areata in a humanized mouse model, suggesting these cells could have potential in managing related autoimmune disorders.

research SFRP2/DPP4 and FMO1/LSP1 Define Major Fibroblast Populations in Human Skin

225 citations , April 2018 in “Journal of Investigative Dermatology”

Two main types of fibroblasts with unique functions and additional subtypes were identified in human skin.

research Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations

418 citations , January 2018 in “Journal of Investigative Dermatology”

This study identified at least four distinct fibroblast populations in adult human skin, each with unique functional properties, suggesting potential therapeutic applications for wound healing and fibrosis-related diseases.

research Skin Wound Healing in Humans and Mice: Challenges in Translational Research

276 citations , December 2017 in “Journal of Dermatological Science”

This review discusses the limitations of animal models, particularly mice, in accurately predicting human skin wound healing outcomes and emphasizes understanding species-specific differences in skin characteristics for better translation to clinical settings.

research Regeneration of Fat Cells from Myofibroblasts During Wound Healing

408 citations , January 2017 in “Science”

This study found that hair follicles in mice and humans can convert wound-related myofibroblasts into adipocytes, suggesting a potential pathway to reduce scar formation by activating BMP signaling.

research Pharmacologic Inhibition of JAK-STAT Signaling Promotes Hair Growth

159 citations , October 2015 in “Science Advances”

This study observed that applying JAK-STAT pathway inhibitors to mouse and human skin led to rapid hair growth by inducing the anagen phase of hair follicles.

research A Guide to Studying Human Hair Follicle Cycling In Vivo

212 citations , September 2015 in “Journal of Investigative Dermatology”

This article presents a comprehensive guide for classifying human hair follicle cycle stages in vivo using scalp xenografts on immunocompromised mice, offering valuable resources for researchers in the field.

research Principles and Mechanisms of Regeneration in the Mouse Model for Wound-Induced Hair Follicle Neogenesis

46 citations , March 2015 in “Regeneration”

This review revisits the mechanisms of wound induced hair follicle neogenesis in mice and concludes that the process involves canonical WNT signaling activated by Fgf9 from γδ T cells, but more research is needed to fully understand its cellular bases.

research Restorative Effect of Hair Follicular Dermal Cells on Injured Human Hair Follicles in a Mouse Model

4 citations , January 2015 in “Experimental Dermatology”

This study developed a humanized scalp model in mice which demonstrated that transplanted cultured human hair follicle dermal cells contributed to the restoration of damaged hair follicles.

research Regenerative Hair Waves in Aging Mice and Extra-Follicular Modulators Follistatin, Dkk1, and Sfrp4

75 citations , March 2014 in “Journal of Investigative Dermatology”

This study found that aging mice experience slower and more fragmented hair cycle waves, but transplanting aged skin to a young host can partially restore hair cycling, implicating extracellular factors.

research The Human Hair: From Anatomy to Physiology

107 citations , December 2013 in “International Journal of Dermatology”

This review summarizes the anatomical and physiological aspects of human hair and its clinical significance, but does not report new research findings.

research Distinct Fibroblast Lineages Determine Dermal Architecture in Skin Development and Repair

1235 citations , December 2013 in “Nature”

This study found that skin fibroblasts in mice arise from two distinct lineages which contribute differently to dermal structure and repair, impacting hair follicle formation during wound healing.

Microenvironmental Reprogramming by Three-Dimensional Culture Enables Dermal Papilla Cells to Induce De Novo Human Hair-Follicle Growth

research Microenvironmental Reprogramming by Three-Dimensional Culture Enables Dermal Papilla Cells to Induce De Novo Human Hair-Follicle Growth

256 citations , October 2013 in “Proceedings of the National Academy of Sciences of the United States of America”

This study found that altering cell culture conditions to form three-dimensional papilla spheroids can restore the ability of human dermal papilla cells to induce hair growth in adult skin.

research Fgf9 From Dermal γδ T Cells Induces Hair Follicle Neogenesis After Wounding

237 citations , June 2013 in “Nature Medicine”

This study found that fibroblast growth factor 9, initially secreted by γδ T cells, plays a key role in modulating hair follicle regeneration in mice after skin wounds.

research A Nude Mouse Model of Hypertrophic Scar Shows Morphologic and Histologic Characteristics of Human Hypertrophic Scar

47 citations , November 2012 in “Wound repair and regeneration”

This study found that grafting split-thickness human skin onto nude mice produces scars that mimic hypertrophic scar characteristics in humans, offering a useful model for studying scar formation and treatments.

research Autoimmune Disease Induction in a Healthy Human Organ: A Humanized Mouse Model of Alopecia Areata

75 citations , October 2012 in “Journal of Investigative Dermatology”

This study developed an animal model that recreates alopecia areata by injecting healthy human skin grafts in immunocompromised mice with peripheral blood mononuclear cells enriched for NKG2D+ and CD56+ cells.

research Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling

499 citations , September 2011 in “Cell”

This study found that intradermal adipocyte lineage cells in mice are necessary and sufficient to activate follicular stem cells, highlighting their role in regulating skin stem cell activity.

research Histologic and Cell Kinetic Studies of Hair Loss and Subsequent Recovery Process of Human Scalp Hair Follicles Grafted onto Severe Combined Immunodeficient Mice

31 citations , August 2000 in “Journal of Investigative Dermatology”

This study found that when human hair follicles were grafted onto mice, they progressed through dystrophic stages and returned to normal growth, with stem cells aiding in recovery.

research Failure of Passive Transfer of Serum From Patients With Alopecia Areata and Alopecia Universalis to Inhibit Hair Growth in Transplants of Human Scalp Skin Grafted Onto Nude Mice

60 citations , February 1992 in “British Journal of Dermatology”

In this study, serum from patients with alopecia areata or universalis did not affect hair growth in transplanted scalp skin grafts on nude mice, despite increased deposition of immunoreactants.