Direct implantation of hair-follicle-associated pluripotent (HAP) stem cells repairs intracerebral hemorrhage and reduces neuroinflammation in mouse model

• Published in: PloS one Vol. 18; no. 1; p. e0280304
• Main Authors: Obara, Koya, Shirai, Kyoumi, Hamada, Yuko, Arakawa, Nobuko, Hasegawa, Ayami, Takaoka, Nanako, Aki, Ryoichi, Hoffman, Robert M., Amoh, Yasuyuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.01.2023; Public Library of Science (PLoS)
• Subjects: Anesthesia; Animal models; Animals; Astrocytes; Autografts; Biology and Life Sciences; Brain; Brain damage; Care and treatment; Cell Differentiation; Cerebral Hemorrhage - metabolism; Cerebral Hemorrhage - therapy; Disease Models, Animal; Edema; Embryo cells; Engineering and Technology; Follicles; Function analysis; Gene expression; Glial cells; Hair; Hair Follicle; Hair follicles; Health aspects; Hemorrhage; Implantation; Inflammation; Interleukin 10; Intracerebral hemorrhage; Medical research; Medicine and Health Sciences; Metastases; Mice; Mice, Inbred C57BL; Mice, Nude; Microglia; Microscopy; Monoclonal antibodies; Neuroinflammatory Diseases; Neuronal-glial interactions; Neurons; Oligodendrocytes; Peripheral nerves; Pluripotency; Pluripotent Stem Cells - metabolism; Proteins; Research and Analysis Methods; Sensorimotor system; Spinal cord injuries; Stem cell transplantation; Stem cells; Sutures; Therapeutics, Experimental; Transforming growth factor-b1; Transplantation; Tumors; Japan; United States > US; Temecula California; Germany
• DOI: 10.1371/journal.pone.0280304
• ISSN: 1932-6203

Intracerebral hemorrhage (ICH) is a leading cause of mortality with ineffective treatment. Hair-follicle-associated pluripotent (HAP) stem cells can differentiate into neurons, glial cells and many other types of cells. HAP stem cells have been shown to repair peripheral-nerve and spinal-cord injury in mouse models. In the present study, HAP stem cells from C57BL/6J mice were implanted into the injured brain of C57BL/6J or nude mice with induced ICH. After allo transplantation, HAP stem cells differentiated to neurons, astrocytes, oligodendrocytes, and microglia in the ICH site of nude mice. After autologous transplantation in C57BL/6J mice, HAP stem cells suppressed astrocyte and microglia infiltration in the injured brain. The mRNA expression levels of IL-10 and TGF-β1, measured by quantitative Real-Time RT-PCR, in the brain of C57BL/6J mice with ICH was increased by HAP-stem-cell implantation compared to the non-implanted mice. Quantitative sensorimotor function analysis, with modified limb-placing test and the cylinder test, demonstrated a significant functional improvement in the HAP-stem-cell-implanted C57BL/6J mice, compared to non-implanted mice. HAP stem cells have critical advantages over induced pluripotent stem cells, embryonic stem cells as they do not develop tumors, are autologous, and do not require genetic manipulation. The present study demonstrates future clinical potential of HAP-stem-cell repair of ICH, currently a recalcitrant disease.