Rolf Hoffmann's research while affiliated with University of British Columbia - Vancouver and other places
Publications (53)
The present invention relates to a method for isolating hair follicle mesenchymal stem cells and to the use thereof for therapy and prophylaxis as well as for cosmetic treatments.
• Alopecia areata (AA) is a reversible, initially patchy hair loss most commonly involving the scalp although other regions of the head, including eyelashes and beard, may also be affected. The disease may sometimes lead to complete baldness of the scalp (alopecia areata totalis) or of the entire body (alopecia areata universalis).
• The course of...
Our objective was to develop clinical practice guidance for the evaluation of hirsutism in premenopausal women. The Skin Academy is led by an international interdisciplinary team of experts, and aims to use the latest scientific and clinical data in selected dermatological diseases, to promote awareness, education and best clinical practice, thus i...
The activation of receptor complexes containing glycoprotein 130 (gp130) identifies the interleukin (IL)-6 cytokine family. We examined members of this family for their expression and activity in hair follicles. Quantitative polymerase chain reaction using mRNA derived from microdissected, anagen-stage human hair follicles and comparison to non-fol...
Two drugs which are approved for the treatment of androgenetic alopecia in women in Germany were compared with regard to their influence on hair growth.
Patients were randomized to group I (n = 52) who used 2% minoxidil solution twice daily for a period of 12 months or to group II (n = 51) who used 0.025% alfatradiol solution once daily for 6 month...
Haare haben für Frauen und Männer eine sehr wichtige Bedeutung. Lange, kräftige und glänzende Haare stehen für Vitalität, Jugend und Gesundheit. Daher fühlen sich viele Männer von Haarausfall gestört und Frauen oft geradezu existenziell bedroht. Andererseits können auch zu viele Haare an der falschen Stelle sehr stören. Im Folgenden werden aktuelle...
Pagetoid cells are large intraepidermal cells which spread intraepidermally. We report a 67-year old Caucasian male, who presented for the first time in 1993 with a long-standing pruritic lesion at the scrotum. He was treated for several years by antiinflammatory ointments. Only in July 2003 was a biopsy taken for the first time. The histopathologi...
Alopecia areata (AA) is an autoimmune hair loss disease, that can be transferred between C3H/HeJ mice by skin grafting. We explored whether AA susceptibility is influenced by the availability of interleukin (IL)-2, a cytokine with leukocyte activating and regulatory properties. Mice heterozygous for a targeted deletion of IL-2 from the histocompati...
Alopecia areata (AA) is a suspected hair follicle specific autoimmune disease. The potential for cell transfer of AA using the C3H/HeJ mouse model was examined. Cells isolated from lymph nodes and spleens of AA-affected mice using magnetic bead conjugated monoclonal antibodies were subcutaneously injected into normal C3H/HeJ recipients. Within 5 wk...
Alopecia areata (AA) is a putative, cell-mediated autoimmune disease of anagen stage hair follicles. Inter- and intra-follicular lymphocytic infiltrates are associated with alopecia that may progress from an initially patchy presentation to extensive, even universal, hair loss. We previously noted in a mouse model of AA that regulatory T cells (Tre...
Hepatocyte growth factor (HGF) is a promoter of hair follicle growth. We examined another HGF family member, macrophage-stimulating protein (MSP), for its hair follicle-modulating properties. Western blotting revealed presence of mature MSP in cultured human dermal papilla (DP) cells and bulbar dermal sheath (DS) cells, but not non-bulbar DS cells....
Alopecia areata (AA) is a putative autoimmune disease of the skin with an inflammatory component that can be treated by the local application of contact sensitizers. Here, we explored whether responsiveness toward diphenylcyclopropenone (DPCP) is reflected by the composition and the activation state of peripheral blood mononuclear cells (PBMCs). PB...
Die Möglichkeiten zur Erforschung der Pathogenese der Alopecia areata und zur Entwicklung neuer Therapieansätze sind beim Menschen aus ethischen Gründen begrenzt. Daher ist die Entwicklung geeigneter Tiermodelle für die Alopecia areata sinnvoll. Mit der Dundee experimental bald rat (DEBR) und der C3H/HeJ-Maus stehen mittlerweile zwei gut charakteri...
Green fluorescent protein (GFP)-expressing wild-type, and nontransgenic mouse vibrissa follicle cells were cultured and implanted to mouse ears and footpads. Dermal papiller (DP)-derived cells and cells from the peribulbar dermal sheath "cup" (DSC) induced new hair follicles in both implanted ears and footpads, while nonbulbar dermal sheath cells d...
Summary Alopecia areata is a common disease, but for ethical reasons it seems difficult to perform large-scale studies to elucidate the pathogenesis and to develop new therapeutic approaches in man. It is therefore helpful to develop appropriate animal models. The Dundee experimental bald rat (DEBR) and the C3H/HeJ mouse are well-established animal...
With our current view of alopecia areata as an autoimmune disease, it is probable that disease development in an individual is dependent on multiple genetic and environmental factors interacting in a complex system. Rodent models afford the opportunity to investigate alopecia areata development and to define the significance of the different factor...
Rodent models of human disease provide an important tool in the investigation of genetic and environmental activation factors, disease pathogenesis, and the development of new and improved treatments. Up to 20% of aged C3H/HeJ mice and 70% of Dundee Experimental Bald Rats (DEBR) develop alopecia areata (AA), a nonscarring, inflammatory hair loss di...
It is the aim of this article to review and appraise available data on treatments for alopecia areata (AA) according to the demands of evidence based medicine. Studies evaluating the efficacy of a treatment for AA should include appropriate controls, use cosmetically acceptable hair regrowth as a parameter for treatment success, include patients wi...
Hair loss or hair thinning is a common complaint in clinical dermatology, and patients seeking advice for hair loss are not necessarily bald. Because the effects of treatment attempts are hard to measure, there is need for a sensitive tool to monitor hair loss and treatment responses. Such a method must be able to analyze the biologic parameters of...
Alopecia areata is suspected to be a T cell-mediated autoimmune disease of the hair follicle, where Fas is expressed on hair follicles and Fas ligand on perifollicular infiltrates. To elucidate whether the Fas/Fas ligand pathway is of pathogenetic significance in alopecia areata, we investigated whether alopecia areata can be induced in Fas-deficie...
Androgenetic alopecia (AGA) is the most common type of hair loss. The relatively strong concordance of the degree of baldness in fathers and sons is not consistent with a simple Mendelian trait, and a polygenic basis is considered to be most likely. So far, the predisposing genes for AGA are unknown and we do not understand the molecular steps invo...
Grafting alopecia areata affected C3H/HeJ mouse skin to littermates induces alopecia areata, but high dietary soy oil reduces alopecia areata susceptibility. Alopecia areata affected and resistant mice were characterized to evaluate possible mechanisms involved in alopecia areata resistance. Of 44 mice that received alopecia areata affected skin gr...
The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
Alopecia areata, an autoimmune disease affecting anagen stage hair follicles, can be induced by grafting spontaneous alopecia areata affected skin to normal-haired C3H/HeJ mice. As the onset of alopecia areata can be significantly retarded by anti-CD44 variant isoform 10 treatment, it was interesting to explore the underlying disease mechanism. Two...
Alopecia areata (AA) is a relatively common reversible hair loss disorder usually manifesting as patchy areas of complete hair loss on the scalp and other body parts that can progress to complete loss of all body hair. This condition is now generally assumed to be an autoimmune disease with the hair follicle (HF) as the principal target tissue. AA...
In this review we summarize the characteristic features of multiple eruptive dermatofibromas based on an analysis of cases in the literature. Many researchers have reported multiple eruptive dermatofibromas diagnosed using the definition of "multiple" as the presence of at least 15 lesions. However, this criterion is arbitrarily chosen and might no...
5 alpha-dihydrotestosterone is known to play a crucial part in the regulation of hair growth and in the development of androgenetic alopecia. 5 alpha-dihydrotestosterone is formed locally within the hair follicle from the systemic precursor testosterone by cutaneous steroid 5 alpha-reductase. Moreover, adrenal steroids such as dehydroepiandrosteron...
Schütter werdendes Haar, Haarverlust (Effluvium) und Haarlosigkeit (Alopezie) sind häufige Probleme in der dermatologischen Sprechstunde. Mit wenigen Ausnahmen ist die Art der zugrunde liegenden Störung des Haarwachstums klinisch diagnostizierbar. Häufig jedoch kommt es vor, dass ein geschildertes Haarproblem vom Arzt kaum nachvollziehbar oder ein...
A murine CD44v10-neutralizing antibody has been reported to impair delayed-type hypersensitivity reactions. Because alopecia areata is characterized by a delayed-type hypersensitivity-like T cell mediated immune response, we addressed the question whether an anti-CD44v10-antibody influences the onset of alopecia areata. Therefore, we used the C3H/H...
T cells play an important role in alopecia areata (AA) because AA can be reinduced by the injection of hair follicle-specific CD8+ T cells into AA scalp biopsies, which were grafted onto scid mice, and the depletion of CD8+ T cells restores hair growth in the Dundee experimental bald rat. Moreover, AA can be transferred by grafting of alopecic skin...
A type of hair loss closely resembling human alopecia areata has been described in C3H/HeJ mice. In order to test the assumed analogy with human alopecia areata, we investigated the efficacy of treatment with the contact allergen squaric acid dibutylester. In 12 C3H/HeJ mice with alopecia areata an allergic contact dermatitis was induced and elicit...
Hair growth depends on a close interaction of different cell populations of the hair follicle. In certain regions of the body, androgens interfere with this highly regulated cooperation in a yet poorly understood manner. The response of hair follicles to androgens can be categorized as androgen-dependent, e.g. in the beard, androgen-sensitive, e.g....
The immune response present in untreated alopecia areata (AA) is characterized by overexpression of ICAM-1 and MHC molecules
on dermal papilla cells of affected hair follicles and by a distinct cytokine pattern. After successful treatment with the
potent contact allergen diphenylcyclopropenone (DCP), adhesion molecules are downregulated and a rever...
Interleukin (IL)-1 has been shown to be a potent inhibitor of hair growth in vitro. We hypothesized that this cytokine might be a decisive factor causing hair loss during the lymphocytic attack in alopecia areata. Neither the intracellular pathways involved in hair growth inhibition mediated by IL-1β nor the signal transduction processes within hai...
At present the induction and elicitation of an ACD with potent contact allergens such as DCP appear to be the most effective, but still not definitively curative, approach in treating extensive forms of AA. Experimental data suggest that cytokines and growth factors such as IL 1 beta are involved in the pathogenesis of AA as well as the therapeutic...
Factors that influence the growth of the anagen hair follicle or initiate the switch to a catagen growth pattern have so far not been definitely determined, but there is increasing evidence that cytokines and growth factors play an important role during these processes. Recently we detected an aberrant in situ expression pattern of cytokines of the...
The immunologic pathways by which a contact dermatitis is able to induce hair regrowth in alopecia areata are not completely understood. Novel studies, however, provided evidence that cytokines may play a pivotal role during the pathogenesis of alopecia areata, and a counteracting cytokine pattern induced by the contact dermatitis may be responsibl...
The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
Kupffer cells are known to produce tumor necrosis factor-α upon stimulation with endotoxin or viruses. This tumor necrosis factor-α synthesis is suppressed by prostaglandin E2 or dexamethasone. Using Northern blotting and reverse transcriptase-polymerase chain reaction, it is demonstrated that endotoxin-induced tumor necrosis factor-α synthesis is...
Interleukin-6 has a variety of biological effects, mainly on the immune system. The regulation of this signal at both the site of production and the site of action is necessary to maintain the organism's homeostasis. In the microenvironment of the hepatic sinusoids, Kupffer cells as resident macrophages are the most potent source of interleukin-6 d...
Although the nature of the noxious signal and the anatomical target in alopecia areas (AA) are still unknown, it has been assumed that CD4+ T lymphocytes surrounding and infiltrating the hair bulb might trigger the hair loss. As these T lymphocytes do not promote cytotoxic activity we hypothesize that AA is triggered by cytokines. Topical immunothe...
Tumor necrosis factor-alpha is an important mediator of various inflammatory and immune responses. Its biological action is crucially dependent on interaction with specific cell surface receptors. Two different receptors for TNF-alpha with molecular masses of 55 and 75 kDa have been described. Here, the presence of a 55 kDa TNF receptor mRNA and th...
Stimulated liver macrophages (Kupffer cells) are known to release a variety of inflammation-related substances, e.g. cytokines, prostanoids, and reactive oxygen intermediates. For instance, exposure of Kupffer cells in vitro to lipopolysaccharide (endotoxin) leads to a strongly enhanced synthesis of the mRNA for tumor necrosis factor-alpha, the rel...
The steady-state levels of extracellular matrix proteins are regulated by the rates of their synthesis and degradation. Metalloproteinases and their specific inhibitors, tissue inhibitor of metalloproteinases-1 and -2 are believed to play a crucial role in extracellular matrix protein degradation. Here we show that the tissue inhibitor of metallopr...
A novel and reliable high-performance liquid chromatography (HPLC) method is described for the purification and quantification of double-stranded DNA. The nucleic acids may be obtained by polymerase chain reaction (PCR) or as restriction fragments from enzymatic cleavage; the separated products are devoid of contaminating material like agarose, eth...
Citations
... Although it can develop AA-like hair loss spontaneously-albeit unpredictably-in old age (21), it can be induced to develop AA at a higher rate via a full-thickness skin graft from an affected donor mouse (22,23). It has also been found that AA can be induced by transferring cultured cells isolated from skin-draining lymph nodes in affected mice, providing evidence that AA is a cell-mediated disease (24). ...
Reference: Pathomechanisms of immune-mediated alopecia
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... Various growth factors and cytokines are secreted from DPCs, which act as potent mitogenic factors and play important roles in follicular development and vasculogenesis. The resultant effects of growth factors and cytokines on proliferation of cultured DPCs and other mechanistic arms have been studied by researchers [109][110][111][112][113][114][115][116][117][118][119][120][121][122]. ...
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... TGF-β1) [22]. Apart from this study, several studies have reported an increased level of IFN-γ232425. The reason for this discrepancy is unclear but the source of the samples used for analysis was different between these studies (serum and PBMCs). ...
... 4 The short period of time for the appearance of lesions is more important than the number of lesions. 5 MEDF have been reported in the setting of autoimmune disease, patients treated with immunosuppressive drugs and in the course of HIV infection or neoplasms. 1 ...
... Hair follicle damage is mediated by CD8 ϩ T cells, but a specific contribution of CD4 ϩ and CD8 ϩ T cells is suggested, and transfer studies in the mouse model point toward a major contribution of Th cells [7,9]. AA has been described originally as a Th1-mediated autoimmune disease, where IFN-␣, IFN-␥, TNF-␣, MIF, and IL-1 are of functional importance [6,10,11] and a deficit in the Th1 cytokines, IFN-␥ and IL-2, decreases the frequency of AA in C3H/ HeJ mice [12]. Yet, AA induction is not exclusively based on Th1 cytokine overexpression, as mice with a selective IL-10 deficit are also AA-resistant [13]. ...
... Whereas both statins and ezetimibe are cholesterol-lowering therapies, the hair growth restoration observed in AA patients is most likely to occur as a result of both the immunomodulatory activity of these drugs and their inhibitory activity against the JAK/ STAT pathway. [19] Infiltration of CD4 + and CD8 + lymphocytes is a key feature of AA. [186] CD4 + lymphocytic infiltration increases the expression of intercellular adhesion molecule-1 (ICAM-1) and ...
... Steroid sulfatase (STS) in the dermal papillae of human terminal hair follicles hydrolyzes dehydroepiandrosterone sulfate (DHEAS) to dehydroepiandrosterone (DHEA). In healthy human occipital scalp, as well as in the beard, STS activity was significantly higher in the hair dermal papillae than in the outer root sheaths [41]. ...
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... Also, DPCP immunotherapy is an option for treating recalcitrant AT/AU (11). The exact therapeutic mechanism of DPCP has not yet been elucidated; however, antigenic competition and decreased production of anti-hair-follicle antibodies are thought to play important roles (22). The success rate of DPCP as a treatment of AT/AU ranges from 22% to 79% (11). ...
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... After DPCP treatment, IL-10 was reported to be increased in scalp tissues 23 , and a continuous increase in the expression of IL-10 in peripheral blood mononuclear cells was observed than controls, whereas this was not observed for IL-12 or IFN-gamma 12 . However, some consider AA relatively restrained in IL-10 knockout mice, which suggests IL-10 acts to both contain and promote sensitivity to AA 25 . On the other hand, it has also been reported that serum IL-10 levels in AA and controls were no different 9,10 . ...
... Furthermore, although type I IFNs, such as IFN α and β , can stimulate necroptosis in cancer cells and macrophages 47,48 , a single treatment with IFNG also did not affect RIPKs mRNA expression in bovine LSCs. IFNG induces expression of TNF superfamily receptors in several cells 10,49,50 including bovine LSCs 7 , and the combination of TNF and IFNG can stimulate acute apoptosis and luteolysis 7,10,51 . Based on the above findings, we hypothesized that TNF in combination with IFNG can stimulate RIPK-dependent cell death. ...
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