Priming Mobilization of Hair Follicle Stem Cells Triggers Permanent Loss of Regeneration After Alkylating Chemotherapy

August 2019 in “ Nature Communications ”

Jin Yong Kim, Jungyoon Ohn, Ji-Seon Yoon, Bo Mi Kang, Minji Park, Sookyung Kim, Woochan Lee, Sungjoo Hwang, Jong‐Il Kim, Kyu Han Kim, Ohsang Kwon

hair follicle stem cells alkylating chemotherapy busulfan cyclophosphamide PI3K/Akt pathway p53/p38 pathway mitotic catastrophe G2/M checkpoint activation DNA damage

TLDR Chemotherapy causes permanent hair follicle damage by triggering stem cell loss.

The study established a model to understand the permanent loss of hair follicle regeneration following alkylating chemotherapy using human hair follicles treated with busulfan and cyclophosphamide. It was found that quiescent hair follicle stem cells (HFSCs) unexpectedly underwent massive proliferation after busulfan treatment, followed by large-scale apoptosis after cyclophosphamide exposure. This process was mediated by the activation of the PI3K/Akt pathway and cell death driven by the p53/p38 pathway. RNA-seq analysis revealed that HFSCs experienced mitotic catastrophe with G2/M checkpoint activation. The study concluded that the priming mobilization of HFSCs led to their loss of resistance to DNA damage, resulting in a permanent loss of regeneration after chemotherapy.

View this study on nature.com →

Discuss this study in the Community →

Research cited in this study

21 / 21 results

research Anagen Hair Follicle Repair: Timely Regenerative Attempts from Plastic Extra-Bulge Epithelial Cells

18 citations , January 2019 in “Experimental Dermatology”

Certain cells outside the hair follicle's bulge area can quickly regenerate damaged hair follicles, potentially helping to reduce hair loss from cancer treatments.

research Eccrine Sweat Glands Associate With the Human Hair Follicle Within a Defined Compartment of Dermal White Adipose Tissue

36 citations , February 2018 in “British Journal of Dermatology”

Sweat glands and hair follicles are structurally connected within a specific layer of skin fat.

research Epithelial-To-Mesenchymal Stem Cell Transition In A Human Organ: Lessons From Lichen Planopilaris

71 citations , October 2017 in “Journal of Investigative Dermatology”

PPAR-γ agonists like pioglitazone may help manage lichen planopilaris but don't fully reverse scarring.

research Mobilizing Transit-Amplifying Cell-Derived Ectopic Progenitors Prevents Hair Loss from Chemotherapy or Radiation Therapy

38 citations , September 2017 in “Cancer Research”

Boosting certain cell signals can prevent hair loss from cancer treatments.

research Permanent Diffuse Alopecia After Hematopoietic Stem Cell Transplantation in Childhood

16 citations , March 2017 in “Bone Marrow Transplantation”

Some children who had stem cell transplants developed permanent hair loss, especially when treated with a drug called busulphan.

research Modeling Chemotherapy-Induced Hair Loss: From Experimental Propositions Toward Clinical Reality

6 citations , February 2016 in “The journal of investigative dermatology/Journal of investigative dermatology”

A new model using mice with human hair follicles helps better understand hair loss from chemotherapy.

research Hair Follicle Aging Is Driven by Transepidermal Elimination of Stem Cells via COL17A1 Proteolysis

242 citations , February 2016 in “Science”

Hair loss and aging are caused by the breakdown of a key protein in hair stem cells.

research Human Hair Follicle Organ Culture: Theory, Application, and Perspectives

130 citations , August 2015 in “Experimental Dermatology”

Human hair follicle organ culture is a useful model for hair research with potential for studying hair biology and testing treatments.

research Efficacy of Interventions for Prevention of Chemotherapy-Induced Alopecia: A Systematic Review and Meta-Analysis

110 citations , August 2014 in “International journal of cancer”

Scalp cooling significantly reduces chemotherapy-induced hair loss.

research The Human Hair: From Anatomy to Physiology

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

The document concludes that hair is complex, with a detailed growth cycle, structure, and clinical importance, affecting various scientific and medical fields.

research Protection Against Chemotherapy-Induced Alopecia: Targeting ATP-Binding Cassette Transporters in the Hair Follicle

24 citations , November 2013 in “Trends in pharmacological sciences”

Increasing ABC transporters in hair follicles may prevent chemotherapy-induced hair loss.

research Lichen Planopilaris Is Characterized By Immune Privilege Collapse Of The Hair Follicle's Epithelial Stem Cell Niche

220 citations , June 2013 in “The Journal of Pathology”

Lichen planopilaris may be an autoimmune disease causing hair loss due to immune system issues in hair follicles.

research Pathobiology of Chemotherapy-Induced Hair Loss

218 citations , January 2013 in “The Lancet Oncology”

Chemotherapy causes hair loss by damaging hair follicles and stem cells, with more research needed for prevention and treatment.

research Live Imaging of Stem Cell and Progeny Behavior in Physiological Hair-Follicle Regeneration

305 citations , June 2012 in “Nature”

Hair regeneration needs dynamic cell behavior and mesenchyme presence for stem cell activation.

research Hedgehog Signaling Maintains Hair Follicle Stem Cell Phenotype in Young and Aged Human Skin

62 citations , November 2009 in “Aging Cell”

Hedgehog signaling helps keep hair follicle stem cells the same in both young and old human skin.

research The Hair Follicle as a Dynamic Mini-Organ

759 citations , February 2009 in “Current Biology”

Hair follicles are complex, dynamic mini-organs that help us understand cell growth, death, migration, and differentiation, as well as tissue regeneration and tumor biology.

research Six Cases of Permanent Alopecia After Various Conditioning Regimens Commonly Used in Hematopoietic Stem Cell Transplantation

40 citations , September 2007 in “Bone marrow transplantation”

Certain chemotherapy drugs can cause permanent hair loss in stem cell transplant patients.

research Dissecting the Impact of Chemotherapy on the Human Hair Follicle

99 citations , September 2007 in “The American journal of pathology”

Chemotherapy damages hair follicles, causing hair loss and other cellular changes.

research Characterization and Isolation of Stem Cell-Enriched Human Hair Follicle Bulge Cells

550 citations , December 2005 in “The Journal of clinical investigation/The journal of clinical investigation”

Researchers successfully isolated and identified key markers of stem cell-enriched human hair follicle bulge cells.

Chemotherapy-Induced Alopecia in Mice: Induction by Cyclophosphamide, Inhibition by Cyclosporine A, and Modulation by Dexamethasone

research Chemotherapy-Induced Alopecia in Mice: Induction by Cyclophosphamide, Inhibition by Cyclosporine A, and Modulation by Dexamethasone

36 citations , April 1994 in “PubMed”

Cyclosporine A slows down hair loss from chemotherapy in mice, while dexamethasone increases hair loss but speeds up regrowth.

research Effect of X-Irradiation on Differentiating Hair Follicles

12 citations , April 1960 in “The anatomical record”

X-ray exposure affects developing hair follicles.

Related Community Posts Join

6 / 1000+ results

community Best Microneedle Lengths To Stimulate Stem Cells

in Microneedling 18 upvotes 2 years ago

Microneedling with needle lengths of 1.5mm to 2.5mm to stimulate hair follicle stem cells for potential hair growth. Using needles longer than 2.5mm is not recommended due to risk of puncturing veins in the scalp. A dermastamp is suggested over a roller.

community 22 yr asian male 2 year fin results

in Progress Pictures 135 upvotes 2 years ago

The user "Top_Replacement_7777" shared their positive results with finasteride for hair loss. They asked about maintaining their hair with finasteride and the impact of vaping on hair growth. Another user reassured them that vaping wouldn't affect their progress.

community TDM-105795 phase 2 results are in!

in Research/Science 29 upvotes 2 years ago

TDM-105795 showed promising hair growth results, with higher efficacy than placebo and minimal side effects. It activates dormant hair follicle stem cells and may maintain gains without immediate loss, unlike minoxidil.

community Hair cloning, is it true? what’s the name of the clinic?

in Chat 6 upvotes 2 years ago

Hair cloning is still experimental and not yet available. Successful cloning is estimated to be available around 2035.

community "Hair Follicle Stem Cells are quiescent 99% of the time and permanently reside in the hair follicle"

in Research/Science 1391 upvotes 6 months ago

Hair follicles are mostly dormant but can be reactivated with treatments like minoxidil, finasteride, and microneedling. A new drug, PP405, shows promise for hair regrowth but may not be available until 2027-2028.

community PP405 Identity Research

UmbrellaLabsResearch in Research 292 upvotes 6 months ago

PP405 is a potential hair loss treatment that inhibits mitochondrial pyruvate carriers, increasing lactate dehydrogenase activity and stimulating hair follicle stem cells. In a phase 1 trial, 31% of participants showed over 20% hair density increase with PP405 treatment.

Related Research

2 / 2 results

research Regeneration of Hair Follicles Is Modulated by Flightless I (Flii) in a Rodent Vibrissa Model

17 citations , December 2010 in “Journal of Investigative Dermatology”

Flightless I protein affects hair growth, with low levels delaying it and high levels increasing hair length in rodents.

research Trans-Species Hair Growth Induction by Human Hair Follicle Dermal Papillae

66 citations , August 2001 in “Experimental Dermatology”

Human hair follicle cells can grow hair when put into mouse skin if they stay in contact with mouse cells.