Shiro Niiyama

Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral‐nerve injury: An advantageous alternative to ES and iPS cells

The optimal source of stem cells for regenerative medicine is a major question. Embryonic stem (ES) cells have shown promise for pluripotency but have ethical issues and potential to form teratomas. Pluripotent stem cells have been produced from skin cells by either viral‐, plasmid‐ or transposon‐mediated gene transfer. These stem cells have been termed induced pluripotent stem cells or iPS cells. iPS cells may also have malignant potential and are inefficiently produced. Embryonic stem cells may not be suited for individualized therapy, since they can undergo immunologic rejection. To address these fundamental problems, our group is developing hair follicle pluripotent stem (hfPS) cells. Our previous studies have shown that mouse hfPS cells can differentiate to neurons, glial cells in vitro, and other cell types, and can promote nerve and spinal cord regeneration in vivo. hfPS cells are located above the hair follicle bulge in what we have termed the hfPS cell area (hfPSA) and are nestin positive and keratin 15 (K‐15) negative. Human hfPS cells can also differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In the present study, human hfPS cells were transplanted in the severed sciatic nerve of the mouse where they differentiated into glial fibrillary‐acidic‐protein (GFAP)‐positive Schwann cells and promoted the recovery of pre‐existing axons, leading to nerve generation. The regenerated nerve recovered function and, upon electrical stimulation, contracted the gastrocnemius muscle. The hfPS cells can be readily isolated from the human scalp, thereby providing an accessible, autologous and safe source of stem cells for regenerative medicine that have important advantages over ES or iPS cells. J. Cell. Biochem. 107: 1016–1020, 2009.

Human and mouse hair follicles contain both multipotent and monopotent stem cells

No abstract.

Nestin-positive hair follicle pluripotent stem cells can promote regeneration of impinged peripheral nerve injury

Nestin‐positive, keratin 15 (K15)‐negative multipotent hair follicle stem cells are located above the hair follicle bulge. We have termed this location the hair follicle pluripotent stem cell area. We have previously shown that transplantation of nestin‐expressing hair follicle stem cells can regenerate peripheral nerve and spinal cord injuries. In the present study, we regenerated the impinged sciatic nerve by transplanting hair follicle pluripotent stem cells. Human hair follicle stem cells were transplanted around the impinged sciatic nerve of ICR nude (nu/nu) mice. The hair follicle stem cells were transplanted between impinged sciatic nerve fragments of the mouse where they differentiated into glial fibrillary acidic protein‐positive Schwann cells and promoted the recovery of pre‐existing axons. The regenerated sciatic nerve functionally recovered. These multipotent hair follicle stem cells thereby provide a potential accessible, autologous source of stem cells for regeneration therapy of nerves degenerated by compression between bony or other hard surfaces.

Th2 Immune Response Plays a Critical Role in the Development of Nickel-Induced Allergic Contact Dermatitis

Background:The precise roles of T helper (Th)1-type and Th2-type cytokine responses in nickel (Ni)-induced allergic contact dermatitis have not yet been clearly defined. We investigated the involvement of Th2 cytokines in Ni-induced contact hypersensitivity reaction using GATA-3 transgenic (Tg) mice. Methods: A Ni-titanium (Ti) alloy was implanted under the skin of GATA-3 Tg mice. A Ni solution was then injected 1 month after sensitization. The ear swelling response was measured at several time points after the injection; the cytokine levels in the skin were measured at 48 h after injection, and the serum levels of IgE were measured 1 month after injection. In addition, purified CD4+ splenic cells obtained from the GATA-3 Tg mice sensitized with the Ni-Ti alloy were infused into Rag-2–/– mice, and the ear swelling response of these mice after a further challenge with Ni solution was also measured. Results:Marked ear swelling and elevated serum IgE levels and skin tissue levels of IL-4 were observed in Ni-Ti-sensitized GATA-3 Tg mice. The Rag-2–/– mice transfused with the CD4+ splenic cells from the Ni-Ti alloy sensitized GATA-3 Tg mice showed a significantly more pronounced ear swelling response than the control mice. Conclusion: We confirmed the participation of Th2-type immune reactions in Ni-induced allergy using GATA-3 Tg mice.

Aggressive digital papillary adenocarcinoma on the palm with pulmonary metastases

A 41‐year‐old Japanese male had aggressive digital papillary adenocarcinoma with pulmonary metastases. He had an asymptomatic, solitary, dome‐shaped, skin‐colored firm nodule on his left palm for half year. The tumor consisted of multiple lobules of anaplastic epithelial cells with central necrosis. The neoplastic cells were immunohistochemically positive for cytokeratin and S‐100 protein. Two years after the lesion was removed, pulmonary nodular lesions were found on chest X‐ray. On histopathological examination, the pulmonary biopsy specimens showed lobular proliferation of acantholytic tumor cells and some ductal structures associated with papillary projections. Five years after the initial removal of the lesion, the patient was referred to our hospital because of a recurrent skin nodule on his left palm. The recurrent skin tumor was found to have lobular proliferation of anaplastic cells. On immunohistochemistry, the pulmonary metastasis and the palmar skin nodules were identical. The tumor was diagnosed as an aggressive digital papillary adenocarcinoma. This report is a rare case of aggressive digital papillary adenocarcinoma that was diagnosed based on the histopathology of the pulmonary metastases, which showed ductal structures associated with papillary projections.

Dermatological manifestations associated with microscopic polyangiitis

Microscopic polyangiitis (MPA) is a systemic small vessel vasculitis, which, although primarily associated with necrotizing and crescentic glomerulonephritis and pulmonary capillaritis, often has cutaneous and musculoskeltal features. Although the skin is affected in 20–70% of patients, the precise description has been limited. This retrospective study analyzed clinical manifestations in patients of MPA with skin eruptions.

Zosteriform skin involvement of nodal T‐cell lymphoma: A review of the published work of cutaneous malignancies mimicking herpes zoster

A 77‐year‐old Japanese woman initially presented with non‐Hodgkins lymphoma involving her neck, axillary and inguen lymph nodes. She had edematous erythema and nodules limited to the skin in zosteriform distribution on the left side chest wall along the T4–5 dermatome. In addition, since 1970, we have mainly been collecting English‐language articles on malignant skin tumors and skin metastasis described as zosteriform in the title, and we have reviewed a total of 29 cases, including our own. It should be mentioned that 59% of the cases reported had been diagnosed with herpes zoster at the time of the initial examination and that many of them had received drug therapy (e.g. acyclovir). We wish to add the dermatomic eruption mimicking zoster sine herpete to the list of possible presentations of cutaneous malignancies.

Cyclosporine A as treatment of esophageal involvement in dermatomyositis.

We report a case of a 70-year-old man with dermatomyositis complicated by esophageal involvement resistant to corticosteroid therapy. It had serious and potentially life-threatening implications, resulting in impossible oral feeding. This condition was successfully resolved by administration of cyclosporine A.

Detection of human papillomavirus type 16 in Bowen's carcinoma of the toe.

Background  Human papillomavirus (HPV) is known to cause cervical cancer. Because it has been detected in lesions of Bowenoid papulosis, Bowen’s disease, and Bowen’s carcinoma, HPV infection has been implicated in the pathogenesis of these diseases.

Hyperkeratotic lichenified skin lesion of gluteal region

Elderly people may develop typical skin lesions on the superior part and both sides of the anal cleft. Although such skin changes have recently been reported as anosacral cutaneous amyloidosis in primary cutaneous amyloidosis, in our histopathological examinations no amyloid deposition has been detected at the sites of these lesions. Because hyperkeratosis, acanthosis and follicular plugging were seen in all of the cases histopathologically, we think that these skin manifestations are essentially a type of keratinization abnormality instead. We consider this disease to be a type of senile skin change that develops in response to prolonged mechanical irritation.