Hair follicle-associated-pluripotent (HAP) stem cells

Hair follicles contain several kinds of stem cells. One group, called hair follicle-associated‑pluripotent (HAP) stem cells, sits in the bulge region of the follicle and expresses the protein nestin. Laboratory studies show HAP cells can turn into many different cell types — neurons, glial cells (support cells in nerves), skin cells, smooth muscle, heart muscle, pigment cells and more [2,10,19,25]. HAP cells are easy to collect from the scalp, do not require genetic reprogramming, do not form tumors in published studies, and can be frozen (cryopreserved) without losing their ability to become other cells [29]. Animal studies show HAP cells can help repair injured peripheral nerves and partially repair spinal cord damage, and they can be guided in culture to form beating heart muscle tissue [22–27]. These features make HAP cells an attractive, accessible source for personalized regenerative medicine and for long‑term stem cell banking.

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HAP stem cells are a population of immature cells found in the hair follicle bulge — the part of the follicle that acts as a niche for stem cells that renew hair and skin [1,11–14]. They express nestin (a protein often found in neural stem cells) and markers such as CD34, but do not express certain keratinocyte markers (K15-negative), which suggests they are relatively primitive and flexible in what they can become [10,18]. Researchers have shown these cells can produce a wide range of cell types in lab experiments and in animal models.

Plain language: think of HAP cells as local repair cells that live around the hair root. They can be harvested with minimal invasiveness (a hair follicle from the scalp) and coaxed to become different tissues in the lab.

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• HAP cells are concentrated in the bulge area and the upper parts of the follicle. The upper follicle yields more cells capable of becoming heart muscle in experiments [21,25].
• The bulge is a long‑lived stem cell niche that contributes to hair growth cycles and can also supply cells to the surrounding skin when the skin is damaged [1,12,14].

Why this matters for banking: because these cells are accessible in a small skin or scalp sample and can be expanded or cryopreserved, they are a practical candidate for creating a personal stem cell bank for future therapies.

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• Differentiate into multiple cell types in culture: neurons, glial cells, keratinocytes (skin cells), smooth muscle cells, melanocytes (pigment cells), adipocytes (fat), osteocytes (bone), chondrocytes (cartilage), endothelial cells (blood vessels), and cardiac muscle cells [2,3,19,20,25].
• Promote peripheral nerve repair: when transplanted into gaps between severed sciatic nerves in mice, HAP cells became Schwann cells (the cells that wrap nerve fibers), formed myelin, supported regrowth of axons, and improved functional outcomes such as muscle contraction and walking measures [22,23]. Figures in the original studies show HAP-derived cells forming myelin sheaths around axons in joined nerves.
• Help spinal cord recovery: in rodent spinal cord injury models, transplanted HAP cells differentiated into supportive glial/Schwann‑like cells and led to significant improvements on standard locomotor scales (e.g., BBB score), though not full recovery [24,38].
• Form beating heart muscle in vitro: HAP cells cultured with certain signals (isoproterenol, activin A, BMP4, basic FGF) can become troponin‑positive cardiac cells and form sheets of beating muscle; their beating rate responds to drugs that affect heart rate, indicating functional properties [25,26]. Age-related decline in the cardiac differentiation potential has been reported, with early-age cells showing better cardiac potential [27].
• Produce new blood vessels: in mice, some blood vessels in the skin arise from nestin-expressing follicle cells during hair growth, showing a role in vascular formation [18,39].

These results come from multiple research groups and include both mouse and human hair follicle studies [2,10,17,22–30].

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• Human HAP (hHAP) cells have been isolated from the scalp and show expression of stem-cell transcription factors (Nanog, Oct4) and nestin, and they can be coaxed into neurons, glia, skin cells, smooth and cardiac muscle cells in culture [2,28,29].
• In published preclinical models, HAP cells did not form tumors and did not require gene modification (unlike iPS cells), which simplifies safety concerns in theory, though formal clinical safety studies in humans are still needed [29,40].

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A practical advantage: whole hair follicles can be cryopreserved using current slow‑freezing methods and later thawed to recover HAP cells that retain their ability to form different cell types [29]. The work shows nearly the same number of colonies and similar differentiation ability from frozen follicles as from fresh ones. This suggests hair follicles could be banked for personalized regenerative therapies, much like umbilical cord blood or other autologous cell sources.

Implication for longevity and long‑term planning: banking a person’s own HAP cells at a younger age could preserve higher regenerative potential (for example, the ability to form cardiac cells declines with donor age in some reports [27]). A stored autologous supply could be used later to treat nerve injuries, support skin or vascular repair, or potentially for cardiac applications.

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• Most efficacy and safety data come from lab and animal studies. Human clinical trials are needed to confirm benefits and long-term safety.
• There is debate over whether to call these cells "pluripotent" (able to become nearly any cell type) or "multipotent" (able to become a range of related cell types). The authors use "pluripotent" because HAP cells have been shown to produce many lineages, but terminology varies among researchers [17,19,34–36].
• Donor age matters: some differentiation abilities (e.g., to beating cardiac muscle) decrease with age [27], which supports the idea of early collection and banking for future therapeutic use.

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• Accessibility: Hair follicles are a minimally invasive, widely available source of adult stem cells.
• Autologous potential: Because HAP cells can be taken from an individual, stored, and used later, they offer a route to personalized, immune‑matched therapies without genetic reprogramming.
• Safety profile in preclinical work: HAP cells have not shown tumor formation in reported animal studies and do not require the reprogramming steps used for iPS cells, potentially lowering some risks.
• Cryopreservation works: Published studies show good recovery and retained function after freezing whole follicles, supporting the feasibility of a hair follicle stem cell bank [29].
• Timing matters: Younger donor age preserves broader differentiation potential for certain tissues (notably cardiac differentiation) — an argument in favor of earlier collection if banking for future regenerative or longevity purposes [27].

If you are considering stem cell banking as part of a long-term health plan, hair follicle–derived HAP cells are an option to discuss with your clinician or a specialist in cellular therapies. They offer an easily accessible, potentially lower‑risk autologous stem cell source that can be banked for future regenerative uses.

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Multiple laboratories report that nestin‑expressing HAP stem cells from the hair follicle can produce a wide range of cell types, support nerve and spinal cord repair in animals, and be directed to form functional cardiac tissue in vitro [2,10,22–27,29]. Because they are accessible from scalp hair follicles, can be cryopreserved, and have a favorable preclinical safety profile, HAP stem cells are a promising candidate for personalized regenerative medicine and for stem cell banking strategies aimed at future repair or anti‑aging interventions. Human clinical trials will be needed to confirm efficacy and safety in people.

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• Yu H et al., Isolation of a novel population of multipotent adult stem cells from human hair follicles. Am J Pathol. 2006;168:1879–88. [2]
• Amoh Y et al., Multipotent nestin‑positive, keratin‑negative hair follicle bulge stem cells can form neurons. Proc Natl Acad Sci USA. 2005;102:5530–34. [10]
• Amoh Y et al., Implanted hair follicle stem cells form Schwann cells which support repair of severed peripheral nerves. Proc Natl Acad Sci USA. 2005;102:17734–38. [22]
• Amoh Y et al., Multipotent hair follicle stem cells promote repair of spinal cord injury and recovery of walking function. Cell Cycle. 2008;7:1865–69. [24]
• Yashiro M et al., From hair to heart: Hair follicle stem cells differentiate to beating cardiac muscle cells. Cell Cycle. 2015;14:2362–66. [25]
• Kajiura S et al., Cryopreservation of the hair follicle maintains pluripotency of nestin‑expressing stem cells. Tissue Eng Part C Methods. 2015;21:825–31. [29]

(Reference numbers correspond to the original article's reference list.)