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Did you get it lacazette?Comment
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Could something like this potentially reverse scarring alopecia/fibrosis?Comment
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Yes hellovera, here new HF, sebaceous gland and intradermal epidermis are created following the wound.
those Lgr6+ cells looks really promising
"Lgr6 marks the most primitive kind of epidermal stem cell "
"Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin" (HF, SG, IE)
"Isolation and in vitro expansion of Lgr6-positive multipotent hair follicle stem cells"
" Here, we propose a model system utilizing the easily isolatable Leucine-rich repeat-containing G-protein coupled receptor 6 epithelial stem cell (Lgr6+ ESC), native to the hair follicle’s follicular bulge, for a new novel type of stem cell-based therapy for bone regeneration within fracture defects. "
they are safe adult cells, easily isolatable, and can be expanded. They add SVF in their protocol that is also something safe. So this protocol is quite promising at near term
Interestingly, the same surgeons one year ago tried a protocol and transplanted simply Lgr6 ESCs on the wounds with already some good results
And one year later, they built an enhanced protocol (use of seeded scaffolds, and addition of ADSc containing SVF)
the two studies conclusions:
2014:The LGR6+ epithelial stem cells appear to hold great promise for the development of a clinically useful stem cell–based therapy for the repair of full-thickness wounds and hair regeneration.These results indicate that transplantation of LGR6+ epithelial stem cells promotes epithelialization, hair growth, and angiogenesis in tissues destined for scar formation.
2015:LGR6+GFP ESCs are able to undergo proliferation, differentiation and migration on simple collagen-based scaffolding while augmenting in vivo epithelialization, hair growth and angiogenesis within wound beds. The addition of SVF to LGR6+GFP ESC-seeded scaffolding induces an early form of tissue polarization, providing for the first time, a clinically applicable stem cell based construct for the repair of full thickness wounds and hair regeneration.
The protocol is clinically applicable
These type of cells are safe, ADSc aswell, so the waiting time before testing in clinical trials could be not that muchComment
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To me, this is currently the most interesting thing happening.
Followed in no specific order by:
(1) chirstiano's topical
(2) Hairegen
(3) swisstemples protocol
These seem to be our nearest term possibilities.... but it seems like this lgr6 wounding protocol could be used soon... I think it's no different than PRP in terms of safety... so it could be used pretty soon without 10 year clinical trials.Comment
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Did you receive the paper alright lacazette?Comment
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Hey jacob, nope I don't receive anything dude :/ there's an error somewhere ^^
Those lgr6 cells seems to have everything needed within the wound. the same Follica is trying to do/activate but with médications. At near term, It seems more simple to apply these type of cells and let do their job naturally ( and they are safe and easily accessible), than find the safe medication combo for it, when there's a lot of pathways and genes expression involved
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"Since LGR6 is implicated as an R-spondin receptor ), we had a closer look at the expression of Wnt signaling-related genes and found several Wnt-pathway associated genes such as Wnt6, Fzd1, Sox4, Tcf7l2 upregulated in Lgr6PSU cells (Figures 4C and 4D). Interestingly, several genes associated with nerve fiber development, and axon morphogenesis were upregulated in Lgr6PSU cells, such as Alcam, Sema3e, Ntf3, and Nrp1 (Figures 4C and 4D), which suggest an interaction of Lgr6+ cells with nerve fibers, as recently denoted (Liao and Nguyen, 2014).
The most prominently downregulated genes in Lgr6PSU cells were associated with cytokine receptors (Tnfrsf19 and Cxcl12) and negative regulation of BMP signaling (Sostdc1 and Htra1) (Figures 4C and 4D).
Since the Lgr6PSU likely contains a mixture of Lgr6IST and Lgr6SG, also SG-associated genes such as Scd1 were found to be upregulated (Figure 4C).
Many genes that were highly enriched in Lgr6PSU cells have previously been mapped to the isthmus, like parathyroid hormone-related protein (Pthlh) (Cho et al., 2003), neurotrophin-3 (Ntf3) (Botchkarev et al., 1998), Cd44 (Jensen et al., 2008), and CST6 (Veniaminova et al., 2013)."
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This protocol looks fcuking promising I think, they could kill follica hehe
those plastic surgeons/researchers have the 'curing baldness' as one of their main lab research goals, so they surely will and want to try their protocol soon see what it can done
Too bad they don't answer by mail for the moment
If a US member is motivated, he should call them just to ask if there's a possibility to be put on a list for participating on future trials, or something like that ( the link is in page1 with the phone number of 4 of them)
Like that he could get little infos about what they are planning now with their " for the first time clinically applicable protocol" lol and when they will test on humans, if not yetComment
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Many thanks Jacobus
I get it this time
So first concerning what they plan to do now with it, we don't learn more in it than in the abstract
it's the scientific detailed explication of their transplantation study. They detailed each tools, each materials for each step of the protocol they used ,(how they isolated the Lgr6 cells, how and with what they cultured them, then all the détails about the scaffolding part, then the part about SVF, etc), and how they do it, which amount of any substance they used, for each different type of little things, it's really detailed..( it's good cause it can be a base for any researcher/plastic surgeon specialists in the world who could try to replicate this protocol on its own, even add some ameliorations to work on the wound healing or hair regeneration areas. Big companies researchers aswell of course
but also major part of the text is complete details of the materials and instruments they used to make the scientific constatations/confirmations (measurements of everything, each genes expressions, markers,proteins, explained each type of microscope they used,monitoring stuff etc ,etc )
but there are still great things to read! the combo Lgr6cells/scaffold/SVF could be the way to go
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"Concomitantly, the ectoderm derived Leucine-rich repeat-containing G-protein coupled receptor 5 and 6 epithelial stem cells (LGR5+ LGR6+ ESCs) of the follicular bulge are capable of producing all cell lines of the skin and interfollicular epidermis (7-13). It is the interface created between these embryonically distinct epithelial and dermal compartments that gives mammals their skin.
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" Unfortunately, epithelial LGR5+ and LGR6+ ESC populations are often destroyed following severe full-thickness damage to the skin, leaving tissues incapable of producing a viable and self-sustaining epithelial compartment.cellular entities,
Without the ESC focal niche, remaining tissues are left without the regenerative potential to form a functional epithelium, hair follicle or sweat gland (14).
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"Recent discovery of LGR5 and LGR6 as extracellular phenotypic defining markers for proliferating adult epithelial stem cells in mammalian skin and intestine permits enhanced clinical utility in the application of the ESC in regenerative medicine, wound healing, hair restoration and biomedical engineering."
"The LGR6+ ESC of the hair follicular bulge is perhaps the most primitive stem cell of the epidermis, capable not only of producing all cellular lineages of the skin and interfollicular dermis but also found to play a supportive role in the development of nascent hair follicles within embryonic and proliferating tissues (Figure 1a.) (3, 4, 9-13). "
"Previously published literature suggests that successful isolation of the LGR6+ ESC from the adnexal follicular bulge can result in a viable and culture-ready stem cell population, which has shown tremendous promise in the development of tissue engineered functional skin constructs (4, 12). Here, we sought to determine if the LGR6+ ESC could be isolated, expanded in culture and seeded onto a spectrum of acellular scaffolds to augment healing through the migration, proliferation and differentiation of the ESC into a form of functional skin—capable of producing nascent hair follicles (3, 4). "
"These results suggest that a viable LGR6+GFP ESC population can be isolated from full thickness skin, expanded in culture and seeded onto a variety of simple acellular scaffolds. Additionally, the LGR6+GFP ESC population, once bound to matrix substrate, is able to proliferate and migrate on and within the respective matrix."
"Wound beds receiving LGR6+GFP ESC scaffolds, all healed and re-epithelialized completely by day 10, while both burn controls (wound bed) and matrix controls (respective acellular scaffolding + wound bed) did not. Quantifiable validation of nascent hair follicle formation was undertaken using Cytokeratin-17 (KRT17) transcript expression in addition to direct follicle counts (Figure 3b.).
As described by Ito et al., hair follicle neogenesis following wounding parallels embryonic follicular development at the molecular level, leading to the activation and augmentation of KRT17 during hair regeneration.
RT-PCR performed on total RNA from each wound bed indicated that those containing the LGR6+GFP ESC seeded scaffold population had a relative KRT17 expression of 132.76±19.2 when compared to untreated wound beds (3.45±0.13) and matrix controls (7.01±.98) "
"This data suggests that these matrices are all capable of maintaining a proliferating LGR6+GFP ESC population. "
"Previous published studies have described the unique hair shaft producing capability of the LGR6+ ESC when located within or surrounding a wound bed region. Here, we sought to determine if the LGR6+GFP ESC population seeded matrix would provide a full thickness wound, devoid of the follicular bulge, with nascent hair follicle development (Figure 3e). As indicated, those wound beds containing a LGR6+GFP ESC population seeded scaffold were able to produce nascent hair follicles and cystic structures by day 14 while burn wound bed controls and matrix controls remained devoid of hair follicle formation. "
Co-culture of SVF with LGR6+ ESC on Scaffolding Induces A Form of Primitive Tissue
Polarity
"Understanding the necessity of tissue polarization within a functional skin construct (dermal-epidermal junction), we sought to determine if the addition of a mesenchymal stem cell population to the LGR6+ ESC seeded matrix scaffold would alter the cellular behavior of the LGR6+ ESC in vitro.
"These findings indicate that the concomitant application of SVF to a defined LGR6 ESC population, promotes not only sub-population sustainability, proliferation and migration but also the initiation of a polarizing interaction between cells. Capable of directing a form of lineage specific local migration of stem cells and their progeny within a 3D environment, the ESC and MSC entities appear to initiate a primitive dermal-epidermal interface. "
Co-seeded SVF to LGR6+ ESC Scaffolding Augments Pro-angiogenic Transcripts and Analytes.
"The Stromal Vascular Fraction (SVF), which harbors an assortment of MSC/ADSc and progenitors, can be easily isolated, sustained in culture and directed toward endothelial and angiogenic differentiation (30-33). "
"Our results indicate that although the addition of LGR6+GFP ESC and even more so for SVFRFP to biological-based matrix scaffolding, the combination of the two stem cell entities promoted a synergistic effect on transcription of specific pro-angiogenic genes: VEGF-A, VEGF-B, platelet derived growth factor (PDGF), fibroblast growth factor (FGF2), Neuropilin-1, as well as two of the VEGF receptors—VEGFR-1 and VEGFR-2 (Figure 5a.). Subsequent total protein analysis of the in vitro construct utilizing an angiogenic proteome array platform indicated that synergistic protein translation occurred when scaffolds received both stem cell populations for: VEGF-A, VEGF-B, PDGF, FGF2, angiogenin, angiopoietin-1 and angiopoietin-2"
"These results suggest that although LGR6+ ESCs and SVF have been shown to be competent at promoting healing and angiogenesis/vasculogenesis, in both in vitro and living systems, the combination of the two stem cell populations has the capacity to synergistically augment the production of some pro-angiogenic factors, even at halved subpopulation quantities. "
"Here, we present a new method of providing skin to those wound beds that are
intrinsically incapable of healing themselves. This method provides a hybrid graft alternative, which forgoes the classic method of requiring large donor sites of healthy skin in order to provide sufficient cutaneous substrate,[U] by applying the potential of the recently discovered LGR associated epithelial stem cell family.
"The LGR6+ ESC hybrid graft, which simply promotes the natural occurring concept of a scaffold based multi-lineage stem cell population, circumvents those inherent limitations found with both CEA and more basic skin grafts. "
"These LGR6+ ESC seeded scaffold-based results correlate with our prior LGR6+ ESC
delivery studies indicating that the ESC entity is capable of viable delivery through direct wound bed seeding, peri-wound bed injection or through scaffold implantation."
"Without an ESC stem cell niche within a potential preliminary or initial skin construct, any epithelium or temporary epithelial material will lack not only the LGR differential potential, but also the transit amplifying (TA) region that previously published literature has suggested to be imperative for the existence and continuation of highly proliferative and functional epithelium. "Comment
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can someone explain to me what is being discussed here? Like as if I'm 14 yearsold.
I think what I'm reading is. "There is a new method of hair growth"Comment
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