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Updated: Feb 25, 2026

Generation of Integration-free Human Induced Pluripotent Stem Cells Using Hair-derived Keratinocytes
Published on: August 20, 2015
Hair follicle-associated-pluripotent (HAP) stem cells
Yasuyuki Amoh1, Robert M Hoffman2,3
1a Department of Dermatology , Kitasato University School of Medicine , Minami Ward , Sagamihara , Japan.
Hair follicle-associated-pluripotent (HAP) stem cells are the most primitive skin stem cells, capable of regenerating skin and hair follicles. These versatile cells show significant potential for regenerative medicine applications.
Area of Science:
- Dermatology
- Stem Cell Biology
- Regenerative Medicine
Background:
- The skin harbors diverse stem cell populations, including keratinocyte and melanocyte progenitors, skin-derived precursors (SKPs), and nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells.
- HAP stem cells are located in the hair follicle bulge and express the stem cell marker CD34 while being K15-negative, indicating a primitive state.
Purpose of the Study:
- To investigate the potential of HAP stem cells as the most primitive stem cells in the skin.
- To explore the differentiation capabilities and regenerative potential of HAP stem cells.
- To evaluate the suitability of HAP stem cells for regenerative medicine compared to other stem cell types.
Main Methods:
- Characterization of HAP stem cells based on their location, marker expression (CD34, K15), and differentiation potential.
- Assessment of HAP stem cell ability to regenerate skin structures like the epidermis and hair follicle.
- Evaluation of transplanted HAP stem cells in preclinical models for peripheral nerve, spinal cord, and cardiac tissue repair.
Main Results:
- HAP stem cells demonstrated differentiation into various cell types, including nerve cells, glial cells, keratinocytes, smooth muscle cells, cardiac muscle cells, and melanocytes.
- These stem cells possess the capacity to regenerate the epidermis and parts of the hair follicle, suggesting they may be the origin of other skin stem cells.
- Transplanted HAP stem cells facilitated recovery in peripheral nerve and spinal cord injury models and showed potential for heart regeneration.
Conclusions:
- HAP stem cells represent the most primitive stem cells identified in the skin, with broad differentiation and regenerative capabilities.
- Their accessibility, lack of tumor formation, and cryopreservation stability position HAP stem cells as a promising alternative to induced pluripotent stem cells (iPS) and embryonic stem cells (ES) for regenerative medicine.
- HAP stem cells hold significant potential for treating a range of conditions, from skin and hair loss to neurological and cardiac damage.
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