Myofibroblast induction with transforming growth factor-β1 and -β3 in cutaneous fetal excisional wounds

Lanning, David A.; Diegelmann, Robert F.; Yager, Dorne R.; Wallace, Michael L.; Bagwell, Charles E.; Haynes, Jeffrey H.

doi:10.1016/s0022-3468(00)90007-1

Cited by 52 publications

(41 citation statements)

References 18 publications

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“…The stimulation of SMA expression by TGF-PI is consistent with previous observations of the stimulation of myofibroblast differentiation and SMA expression by TGF-PI for fibroblasts isolated from other connective tissues [21,22,24,42]. This is the first study to our knowledge, to demonstrate the capability of TGF-PI to increase expression of SMA in cells migrating from their host tissue onto three-dimensional collagen lattices, or in human ligament cells.…”

Section: Discussionsupporting

confidence: 90%

The effect of selected growth factors on human anterior cruciate ligament cell interactions with a three‐dimensional collagen‐GAG scaffold

Murray

Rice

Wright

et al. 2003

Journal Orthopaedic Research

124

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Our work focuses on development of a collagen-glycosamimoglycan (CC) scaffold to facilitate ligament healing in the gap between the ruptured ends of the human anterior cruciate ligament (ACL). In the present investigation, we evaluated the effects of selected growth factors on human ACL cell responses important in tissue regeneration, namely cell migration, proliferation, collagen production, and expression of a-smooth muscle actin (SMA).Methods: Explants from six human ACLs were cultured on top of a CG scaffold. Culture conditions were with either 2% FBS (control), or 2% FBS supplemented with TGF-01, PDGF-AB, EGF, or FGF-2. Histologic cell distribution, total DNA content, proliferation rate, rate of collagen synthesis, scaffold diameter and percentage of SMA positive cells were determined at two, three and four weeks.Results: The addition of TGF-01 to the culture medium resulted in increased cell number, increased collagen production and increased expression of SMA within the scaffold. Supplementation with PDGF-AB resulted in increased cell proliferation rates within the scaffold and increased collagen production. The addition of FGF-2 resulted in increased cell proliferation rates and slowed rates of scaffold shrinkage when compared with the control group.Discussion: This work suggests that certain growth factors can alter the biologic functions of human ACL cells in a CG scaffold implanted as a bridge at the site of an ACL rupture. Based on these findings, the addition of selected growth factors to an implantable CG scaffold may facilitate ligament healing in the gap between the ruptured ends of the human ACL.

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Section: Discussionsupporting

confidence: 90%

The effect of selected growth factors on human anterior cruciate ligament cell interactions with a three‐dimensional collagen‐GAG scaffold

Murray

Rice

Wright

et al. 2003

Journal Orthopaedic Research

124

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“…They play an essential role in wound healing, including secretion of a series of growth factors that facilitates angiogenesis and matrix deposition (Beldon, 2010;Al-Mulla et al, 2011). Some of the fibroblasts in the injured tissue may differentiate into a highly contractile phenotype, i.e., myofibroblasts (Ross et al, 1970;Gabbiani, 1996),which have bundles of a-smooth muscle actin (SMA) contributing to the closure of wound (Gabbiani, 2003;Lanning et al, 2000). Collagen and fibronectin are important components of granulation tissue, contributing to its integrity and delivery of tethered growth factors (Park et al, 2005;Hamed et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Notoginsenoside Ft1 Promotes Fibroblast Proliferation via PI3K/Akt/mTOR Signaling Pathway and Benefits Wound Healing in Genetically Diabetic Mice

Zhang

Gao

Yang

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Wound healing requires the essential participation of fibroblasts, which is impaired in diabetic foot ulcers (DFU). Notoginsenoside Ft1 (Ft1), a saponin from Panax notoginseng, can enhance platelet aggregation by activating signaling network mediated through P 2 Y 12 and induce proliferation, migration, and tube formation in cultured human umbilical vein endothelial cells. However, whether it can accelerate fibroblast proliferation and benefit wound healing, especially DFU, has not been elucidated. In the present study on human dermal fibroblast HDF-a, Ft1 increased cell proliferation and collagen production via PI3K/Akt/ mTOR signaling pathway. On the excisional wound splinting model established on db/db diabetic mouse, topical application of Ft1 significantly shortened the wound closure time by 5.1 days in contrast with phosphate-buffered saline (PBS) treatment (15.8 versus 20.9 days). Meanwhile, Ft1 increased the rate of reepithelialization and the amount of granulation tissue at day 7 and day 14. The molecule also enhanced mRNA expressions of COL1A1, COL3A1, transforming growth factor (TGF)-b1 and TGF-b3 and fibronectin, the genes that contributed to collagen expression, fibroblast proliferation, and consequent scar formation. Moreover, Ft1 facilitated the neovascularization accompanied with elevated vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor at either mRNA or protein levels and alleviated the inflammation of infiltrated monocytes indicated by reduced tumor necrosis factor-a and interleukin-6 mRNA expressions in the diabetic wounds. Altogether, these results indicated that Ft1 might accelerate diabetic wound healing by orchestrating multiple processes, including promoting fibroblast proliferation, enhancing angiogenesis, and attenuating inflammatory response, which provided a great potential application of it in clinics for patients with DFU.

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“…Provided that healing was being studied at a sufficiently early stage of the gestation period, investigators observed lack of contraction of untreated, excisional skin wounds in the rabbit; instead, significant wound expansion was documented in three rabbit studies (Ledbetter et al 1991;Lanning et al 1999Lanning et al , 2000. At sufficiently late stages of the gestation period, or following appropriate manipulation, investigators reported healing with contraction in excisional skin wounds in the foetal rabbit (Lanning et al 1999(Lanning et al , 2000 and foetal lamb models (Longaker et al 1991a,b;Horne et al 1992;Stelnicki et al 2000). Quantitative data obtained with an amphibian model showed that, prior to metamorphosis (tadpole stages), the contribution of contraction to skin wound closure continuously increased at the expense of regeneration while scar formation was negligible; after metamorphosis (frog), contraction dominated over scar formation while regeneration was undetectable (Yannas et al 1996).…”

Section: Two Current Views Of the Ontogenetic Transition From Scarlesmentioning

confidence: 99%

Similarities and differences between induced organ regeneration in adults and early foetal regeneration

Yannas

2005

J. R. Soc. Interface.

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At least three organs (skin, peripheral nerves and the conjunctiva) have been induced to regenerate partially in adults following application of porous, degradable scaffolds with highly specific structure (templates). Templates blocked contraction and scar formation by inducing a reduction in the density of contractile fibroblasts (probably myofibroblasts) and by preventing these cells to organize themselves appropriately in the wound. In contrast, during early foetal healing, myofibroblasts were absent and wounds did not close by contraction but rather by spontaneous regeneration. The adult regenerative process has so far led to imperfect recovery of the physiological anatomy of skin (skin appendages were missing), while early foetal healing has led to apparently complete restoration. Furthermore, the mechanism of the adult regenerative process involves thwarting of myofibroblast function while, during early foetal healing, differentiation of myofibroblasts has not yet occurred. The data suggest that induced organ regeneration in the adult is the result of partial reversion to early foetal healing. If so, the adult may conceal a foetal response that may be subject to activation following application of highly active scaffolds or of other substances or cells.

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Myofibroblast induction with transforming growth factor-β1 and -β3 in cutaneous fetal excisional wounds

Cited by 52 publications

References 18 publications

The effect of selected growth factors on human anterior cruciate ligament cell interactions with a three‐dimensional collagen‐GAG scaffold

The effect of selected growth factors on human anterior cruciate ligament cell interactions with a three‐dimensional collagen‐GAG scaffold

Notoginsenoside Ft1 Promotes Fibroblast Proliferation via PI3K/Akt/mTOR Signaling Pathway and Benefits Wound Healing in Genetically Diabetic Mice

Similarities and differences between induced organ regeneration in adults and early foetal regeneration

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