Cellular Level Modeling Predicts Hair Follicle Growth Via Stem Cells

Your hair or lack of will be the direct result of the lifelong tug-of-war in between activators that wake up, and cellular inhibitors that “calm” the stem cells in each and every hair follicle on your Body.  According to Dr Cheng-Ming Chuong of USC and his colleagues from Oxford University Dr Ruth Baker and Dr Philip Maini, the understanding of of “cellular automaton” model is crucial in helping describe the group behavior of hair follicles.The researchers discovered that every adult hair follicle can count only on their inherent growth-promoting signals, with out the assist of adjacent follicles within the macro-environment. In contrast to the growth promotion in Humans, the growth of rabbit and mice hair follicles will be dependent on signals from neighborly follicles.

The new cellular level automaton model consists of a normal grid of automation 1 hair follicle  with 4 distinct and functional cyclic stages. He also noted that Surrounding every automaton are 8 automata, which are the hair follicle’s neighbors.According to the stem cell blog website, Every automaton stage and modifications are based on guidelines that

Dr Cheng Ming Chuong

dictate if or not hair on human scalps or in animal’s fur coats will be caught up in large waves of growth known as the anagen phase, or stay within the telogen or resting phase. Under proper circumstances such as the winter season or a new physiological and/or developmental stage in an organism’s life like puberty for example, an amazing collective regeneration wave can sweep over your skin, activating all the hair stem cells in the individual follicles and even those in front of them, by the 10′s of thousands.

In other life stages, some individual hair follicles might even stay locked into the telogen stage by the inhibitors in their own macro-environment. The Inhibitor levels are carefully modulated in component by intradermal adipose tissue and also the central endocrine method. These numerous layers of manage produce a balance in between the inhibitory bone morphogenic protein or BMP. This is a signal that keeps hair stem cells in a calm quiescent state and later activating then with signals that wake them up.

The groundbreaking new information introduces a new method to treating androgenic alopecia, probably the most common type of hair loss or alopecia in most aging males: It may be simpler to obtain hair follicles expand them once more by enhancing their surrounding atmosphere, instead of the traditional stem cell treatments for hair loss.

L-Ascorbic acid 2-phosphate promotes IGF-1 expression and stimulates hair follicle growth

Abstract

BACKGROUND:

l-Ascorbic acid 2-phosphate (Asc 2-P), a derivative of l-ascorbic acid, promotes elongation of hair shafts in cultured human hair follicles and induces hair growth in mice.

OBJECTIVES:

To investigate whether the promotion of hair growth by Asc 2-P is mediated by insulin-like growth factor-1 (IGF-1) and, if so, to investigate the mechanism of the Asc 2-P-induced IGF-1 expression.

METHODS:

Dermal papilla (DP) cells were cultured and IGF-1 level was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay after Asc 2-P treatment in the absence or presence of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Also, hair shaft elongation in cultured human scalp hair follicles and proliferation of cocultured keratinocytes were examined after Asc 2-P treatment in the absence or presence of neutralizing antibody against IGF-1. In addition, keratinocyte proliferation in cultured hair follicles after Asc 2-P treatment in the absence or presence of LY294002 was examined by Ki-67 immunostaining.

RESULTS:

IGF-1 mRNA in DP cells was upregulated and IGF-1 protein in the conditioned medium of DP cells was significantly increased after treatment with Asc 2-P. Immunohistochemical staining showed that IGF-1 staining is increased in the DP of cultured human hair follicles by Asc 2-P. The neutralizing antibody against IGF-1 significantly suppressed the Asc 2-P-mediated elongation of hair shafts in hair follicle organ culture and significantly attenuated Asc 2-P-induced growth of cocultured keratinocytes. LY294002 significantly attenuated Asc 2-P-inducible IGF-1 expression and proliferation of follicular keratinocytes in cultured hair follicles.

CONCLUSIONS:

These data show that Asc 2-P-inducible IGF-1 from DP cells promotes proliferation of follicular keratinocytes and stimulates hair follicle growth in vitro via PI3K.

PMID:

19416266

[PubMed – indexed for MEDLINE]

Grow eyelashes with bimatoprost (Latisse)

Abstract

OBJECTIVE:

To evaluate a bimatoprost gel for enhancing eyelash growth, adverse effects, and change in intraocular pressure (IOP).

METHODS:

Prospective, double-masked, randomized controlled study. Fifty-two patients without ocular disease were assigned a control or bimatoprost 0.03% gel to apply to the eyelid margin once a day.

RESULTS:

The adjusted mean change in eyelash length from baseline to 6 months was 0.77 mm in the bimatoprost group and -0.12 mm in the control group (P = 0.004). Adverse effects were experienced by 2 of 16 patients (12.5%) in the control group and 9 of 36 patients (25%) in the bimatoprost gel group. Mean change in IOP from baseline to 6 months was 0.685 mmHg in the control group and -2.04 mmHg in the bimatoprost group (P = 0.009).

CONCLUSIONS:

Bimatoprost gel was effective in enhancing eyelash growth. The most common adverse effect for the bimatoprost gel was conjunctival and eyelid hyperemia, while the most severe was recurrent anterior uveitis. Mean IOP was reduced in subjects using the bimatoprost gel.

PMID:

20618554

[PubMed – indexed for MEDLINE]

Insulin and IGF-1 are important hair growth promoters – new candidates in the fight against hair loss?

Effects of insulin and insulin-like growth factors on cultured human hair follicles: IGF-I at physiologic concentrations is an important regulator of hair follicle growth in vitro.

Philpott MP, Sanders DA, Kealey T.

Source

Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, U.K.

Abstract

Insulin stimulated hair follicle growth in a dose-dependent manner over the range of 0.01 to 100 micrograms/ml. Maximum rates of hair follicle growth were observed when follicles were maintained in medium containing 10 micrograms/ml insulin, which is supraphysiologic. Hair follicles maintained in the absence of insulin or at physiologic levels showed premature entry into a catagen-like state. Insulin-like growth factor (IGF)-I and -II had no significant effect on hair follicle growth when maintained in the presence of 10 micrograms/ml insulin. However, in the absence of insulin, both IGF-I (0.01-100 ng/ml) and IGF-II (0.01-100 ng/ml) stimulated hair follicle growth in a dose-dependent manner. IGF-I was more potent than either insulin or IGF-II, stimulating maximum rates of hair follicle growth at 10 ng/ml, whereas IGF-II gave maximum stimulation at 100 ng/ml. The rates of hair follicle growth stimulated by 10 ng/ml IGF-I were identical to those stimulated by 10 micrograms/ml insulin. IGF-II (100 ng/ml), however, was unable to stimulate hair follicle growth to the same extent as insulin. Both IGF-I (10 ng/ml) and IGF-II (100 ng/ml) were more potent than insulin at preventing hair follicles from entering into a catagen-like state. Growth hormone had no effect on hair follicle growth or morphology in the absence of insulin. These data suggest that in vitro IGF-I may be an important physiologic regulator of hair growth and possibly the hair growth cycle. Moreover, the removal of insulin from tissue culture medium may be a useful method of generating large numbers of catagen hair follicles for further in vitro studies.

PMID:

8006448

[PubMed – indexed for MEDLINE]

Raspberry extract on your skin and head – combat baldness and rejuvenate your skin, as it raises IGF-1 levels

BUY IGF-1 LR3 or DES-IGF FROM US! superhumangear@gmail.com

Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans.

Harada N, Okajima K, Narimatsu N, Kurihara H, Nakagata N.

Source

Department of Translational Medical Science Research, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.

Abstract

Sensory neurons release calcitonin gene-related peptide (CGRP) on activation. We recently reported that topical application of capsaicin increases facial skin elasticity and promotes hair growth by increasing dermal insulin-like growth factor-I (IGF-I) production through activation of sensory neurons in mice and humans. Raspberry ketone (RK), a major aromatic compound contained in red raspberries (Rubus idaeus), has a structure similar to that of capsaicin. Thus, it is possible that RK activates sensory neurons, thereby increasing skin elasticity and promoting hair growth by increasing dermal IGF-I production. In the present study, we examined this possibility in mice and humans. RK, at concentrations higher than 1 microM, significantly increased CGRP release from dorsal root ganglion neurons (DRG) isolated from wild-type (WT) mice and this increase was completely reversed by capsazepine, an inhibitor of vanilloid receptor-1 activation. Topical application of 0.01% RK increased dermal IGF-I levels at 30 min after application in WT mice, but not in CGRP-knockout mice. Topical application of 0.01% RK increased immunohistochemical expression of IGF-I at dermal papillae in hair follicles and promoted hair re-growth in WT mice at 4 weeks after the application. When applied topically to the scalp and facial skin, 0.01% RK promoted hair growth in 50.0% of humans with alopecia (n=10) at 5 months after application and increased cheek skin elasticity at 2 weeks after application in 5 females (p<0.04). These observations strongly suggest that RK might increase dermal IGF-I production through sensory neuron activation, thereby promoting hair growth and increasing skin elasticity.

PMID:

18321745

[PubMed – indexed for MEDLINE]

Copper peptide (ghk-Cu tripeptide-1) for hair growth

Chemical agents and peptides affect hair growth

Uno H, Kurata S.

Source

Wisconsin Regional Primate Research Center, Madison 53715-1299.

Abstract

During the past decade we have examined both the therapeutic and the prophylactic effects of several agents on the macaque model of androgenetic alopecia. Minoxidil and diazoxide, potent hypotensive agents acting as peripheral vasodilators, are known to have a hypertrichotic side effect. Topical use of both agents induced significant hair regrowth in the bald scalps of macaques. The application of a steroid 5 alpha-reductase inhibitor (4MA) in non-bald preadolescent macaques has prevented baldness, whereas controls developed it during 2 years of treatment. The effects of hair growth were determined by 1) phototrichogram, 2) folliculogram (micro-morphometric analysis), and 3) the rate of DNA synthesis in the follicular cells. These effects were essentially a stimulation of the follicular cell proliferation, resulting in an enlargement of the anagen follicles from vellus to terminal type (therapy) or a maintenance of the prebald terminal follicles (prevention). A copper binding peptide (PC1031) had the effect of follicular enlargement on the back skin of fuzzy rats, covering the vellus follicles; the effect was similar to that of topical minoxidil. Analyzing the quantitative sequences of follicular size and cyclic phases, we speculate on the effect of agents on follicular growth. We also discuss the triggering mechanism of androgen in the follicular epithelial-mesenchymal (dermal papilla) interaction.

>Thyroid hormones directly alter human hair follicle functions: regrowth and pigmentation

>Thyroid hormones directly alter human hair follicle functions: anagen prolongation and stimulation of both hair matrix keratinocyte proliferation and hair pigmentation

van Beek N, Bodó E, Kromminga A, Gáspár E, Meyer K, Zmijewski MA, Slominski A, Wenzel BE, Paus R.

Department of Dermatology, University Hospital Schleswig-Holstein, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.

Abstract

CONTEXT: Both insufficient and excess levels of thyroid hormones (T3 and T4) can result in altered hair/skin structure and function (e.g. effluvium). However, it is still unclear whether T3 and T4 exert any direct effects on human hair follicles (HFs), and if so, how exactly human HFs respond to T3/T4 stimulation.

OBJECTIVE: Our objective was to asses the impact of T3/T4 on human HF in vitro.

METHODS: Human anagen HFs were isolated from skin obtained from females undergoing facelift surgery. HFs from euthyroid females between 40 and 69 yr (average, 56 yr) were cultured and treated with T3/T4.

RESULTS: Studying microdissected, organ-cultured normal human scalp HFs, we show here that T4 up-regulates the proliferation of hair matrix keratinocytes, whereas their apoptosis is down-regulated by T3 and T4. T4 also prolongs the duration of the hair growth phase (anagen) in vitro, possibly due to the down-regulation of TGF-beta2, the key anagen-inhibitory growth factor. Because we show here that human HFs transcribe deiodinase genes (D2 and D3), they may be capable of converting T4 to T3. Intrafollicular immunoreactivity for the recognized thyroid hormone-responsive keratins cytokeratin (CK) 6 and CK14 is significantly modulated by T3 and T4 (CK6 is enhanced, CK14 down-regulated). Both T3 and T4 also significantly stimulate intrafollicular melanin synthesis.

CONCLUSIONS: Thus, we present the first evidence that human HFs are direct targets of thyroid hormones and demonstrate that T3 and/or T4 modulate multiple hair biology parameters, ranging from HF cycling to pigmentation.

PMID: 18728176 [PubMed – indexed for MEDLINE]

FULL ARTICLE IN PDF

>Hair growth effect of minoxidil

>

Pharmacological Evaluation Laboratory, Taisho Pharmaceutical Co., Ltd., 403, Yoshino-cho 1-chome, Saitama-shi, Saitama 330-8530, Japan.

Abstract

The length and size of hair are depend on the anagen term in its hair cycle. It has been reported that the some cell growth factors, such as VEGF, FGF-5S, IGF-1 and KGF, induce the proliferation of cells in the matrix, dermal papilla and dermal papillary vascular system and increase the amount of extra cellular matrix in dermal papilla and then maintain follicles in the anagen phase. On the other hand, negative factors, like FGF-5, thrombospondin, or still unknown ones, terminate the anagen phase. If the negative factors become dominant against cell proliferation factors according to fulfilling some time set by the biological clock for hair follicles, TGF beta induced in the matrix tissues evokes apoptosis of matrix cells and shifts the follicles from anagen to catagen. Androgenetic alopecia is caused by miniaturizing of hair follicles located in the frontal or crown part of scalp and are hereditarily more sensitive to androgen. In their hair cycles, the androgen shortens the anagen phase of follicles and shifts them to the catagen phase earlier than usual. The mode of action of hair growth effect of minoxidil is not completely elucidated, but the most plausible explanation proposed here is that minoxidil works as a sulfonylurea receptor (SUR) activator and prolongs the anagen phase of hair follicles in the following manner: minoxidil (1) induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupled SUR on the plasma membrane of dermal papilla cells, (2) inhibits of TGF beta induced apoptosis of hair matrix cells by opening the Kir 6.0 channel pore coupled with SUR on the mitochondrial inner membrane, and (3) dilates hair follicle arteries and increases blood flow in dermal papilla by opening the Kir 6.0 channel pore coupled with SUR on the plasma membrane of vascular smooth muscle cells.

PMID: 11915519 [PubMed – indexed for MEDLINE]

>L-carnitine-L-tartrate promotes human hair growth

>

L-carnitine-L-tartrate promotes human hair growth in vitro

The trimethylated amino acid l-carnitine plays a key role in the intramitochondrial transport of fatty acids for beta-oxidation and thus serves important functions in energy metabolism. Here, we have tested the hypothesis that l-carnitine, a frequently employed dietary supplement, may also stimulate hair growth by increasing energy supply to the massively proliferating and energy-consuming anagen hair matrix. Hair follicles (HFs) in the anagen VI stage of the hair cycle were cultured in the presence of 0.5-50 microm of l-carnitine-l-tartrate (CT) for 9 days. At day 9, HFs treated with 5 microm or 0.5 microm of CT showed a moderate, but significant stimulation of hair shaft elongation compared with vehicle-treated controls (P < 0.05). Also, CT prolonged the duration of anagen VI, down regulated apoptosis (as measured by TUNEL assay) and up regulated proliferation (as measured by Ki67 immunohistology) of hair matrix keratinocytes (P < 0.5). By immunohistology, intrafollicular immunoreactivity for TGFbeta2, a key catagen-promoting growth factor, in the dermal papilla and TGF-beta II receptor protein in the outer root sheath and dermal papilla was down regulated. As shown by caspase activity assay, caspase 3 and 7, which are known to initiate apoptosis, are down regulated at day 2 and day 4 after treatment of HFs with CT compared with vehicle-treated control indicating that CT has an immediate protective effect on HFs to undergo programmed cell death. Our findings suggest that l-carnitine stimulates human scalp hair growth by up regulation of proliferation and down regulation of apoptosis in follicular keratinocytes in vitro. They further encourage one to explore topical and nutraceutical administration of l-carnitine as a well-tolerated, relatively safe adjuvant treatment in the management of androgenetic alopecia and other forms of hair loss.

PMID: 17927577 [PubMed – indexed for MEDLINE]