CoChat
Sign Up
Cited by 83

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Reduction of Fibrosis and Scar Formation by Partial Reprogramming In Vivo

Doeser, Markus C., Schöler, Hans R., Wu, Guangming·2018·Stem Cells
DOI 10.1002/stem.2842
Open this paper in CoChat — free account

Abstract

Transient expression of the transcription factors OCT4, SOX2, KLF4, and C-MYC (OSKM) to induce partial reprogramming while avoiding the pluripotent state and teratoma formation has recently been discussed as a strategy for regenerating damaged tissues in vivo, whereby the impact of partial reprogramming on tissue repair remains to be elucidated. Here, we activated OSKM transcription factors in cutaneous wounds of OSKM-inducible transgenic mice and found that induction of OSKM factors in excisional wounds caused a diminished fibroblast transdifferentiation to myofibroblasts and wound contraction. Gene expression analyses showed downregulation of the profibrotic marker genes transforming growth factor beta 1, Collagen I, and vascular endothelial growth factor. Consequently, histological analyses demonstrated that OSKM induction in incisional wounds resulted in reduced scar tissue formation. These data provide proof of concept that OSKM-mediated partial reprogramming in situ can diminish fibrosis and improve tissue healing with less scar formation without the risk of tumor formation. This new insight into the effects of partial reprogramming in vivo may be relevant for developing reprogramming-based regenerative therapies for tissue injury and fibrotic diseases.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/stem.2842

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In local OSKM wound treatment, the cell types responsible for rejuvenation cannot be uniquely identified because of the heterogeneous composition of the skin at the cellular level.

    “despite the induction being local, the cell types responsible for the rejuvenation cannot be uniquely identified because of the heterogeneous composition of the skin at the cellular level.”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [109]

    The Abstract and Discussion (page unavailable) describe local OSKM induction in cutaneous wounds and reduced scarring. The paper does not say that skin-cell heterogeneity prevents identification of the cells responsible for rejuvenation; its in vitro results instead examine OSKM effects on fibroblasts specifically. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • There are a few instances in which transient reprogramming is beneficial also during the process of tissue repair (and not only prior to the injury), as in traumatic brain injury and skin wound healing.

    “There are a few instances in which transient reprogramming is beneficial also during the process of tissue repair (and not only prior to the injury). This is the case for traumatic brain injury 221 and skin wound healing 222 .”

    From Hallmarks of aging: An expanding universe (2023) · cites this paper as [222]

  • Local and transient exposure of cutaneous wounds to OSKM significantly reduced fibrosis.

    “local and transient factor exposure to cutaneous wounds significantly reduced fibrosis 109 .”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [109]

  • The reduction in fibrosis by local OSKM was due to diminished fibroblast-to-myofiber differentiation, promoting healing and reducing scar formation.

    “the observed effects were due to diminished fibroblast-to-myofiber differentiation, promoting healing and concomitantly reducing scar formation.”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [109]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 51

  1. Takahashi, 2006, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors, Cell, 126, 663, 10.1016/j.cell.2006.07.024 · DOI · Paper page
  2. Lázaro, 2017, Transient transcription factor (OSKM) expression is key towards clinical translation of in vivo cell reprogramming, EMBO Mol Med, 9, 733, 10.15252/emmm.201707650 · DOI
  3. Abad, 2013, Reprogramming in vivo produces teratomas and iPS cells with totipotency features, Nature, 502, 340, 10.1038/nature12586 · DOI · Paper page
  4. Gao, 2016, In vivo reprogramming reactive glia into iPSCs to produce new neurons in the cortex following traumatic brain injury, Sci Rep, 6, 22490, 10.1038/srep22490 · DOI · Paper page
  5. Gurtner, 2008, Wound repair and regeneration, Nature, 453, 314, 10.1038/nature07039 · DOI · Paper page
  6. Martin, 1997, Wound healing–aiming for perfect skin regeneration, Science, 276, 75, 10.1126/science.276.5309.75 · DOI
  7. Zuijlen, 2003, Collagen morphology in human skin and scar tissue: No adaptations in response to mechanical loading at joints, Burns, 29, 423, 10.1016/S0305-4179(03)00052-4 · DOI
  8. Martin, 2004, Parallels between tissue repair and embryo morphogenesis, Development, 131, 3021, 10.1242/dev.01253 · DOI
  9. Grinnell, 1994, Fibroblasts, myofibroblasts, and wound contraction, J Cell Biol, 124, 401, 10.1083/jcb.124.4.401 · DOI
  10. Desmoulière, 2005, Tissue repair, contraction, and the myofibroblast, Wound Repair Regen, 13, 7, 10.1111/j.1067-1927.2005.130102.x · DOI · Paper page
  11. Werner, 2007, Keratinocyte-fibroblast interactions in wound healing, J Invest Dermatol, 127, 998, 10.1038/sj.jid.5700786 · DOI
  12. Hinz, 2007, The myofibroblast: One function, multiple origins, Am J Pathol, 170, 1807, 10.2353/ajpath.2007.070112 · DOI · Paper page
  13. Baum, 2011, Fibroblasts and myofibroblasts: What are we talking about?, J Cardiovasc Pharmacol, 57, 376, 10.1097/FJC.0b013e3182116e39 · DOI
  14. Wilgus, 2008, Regulation of scar formation by vascular endothelial growth factor, Lab Invest, 88, 579, 10.1038/labinvest.2008.36 · DOI
  15. Bullard, 2003, Fetal wound healing: Current biology, World J Surg, 27, 54, 10.1007/s00268-002-6737-2 · DOI
  16. Rowlatt, 1979, Intrauterine wound healing in a 20 week human fetus, Virchows Arch A Pathol Anat Histol, 381, 353, 10.1007/BF00432477 · DOI
  17. Wilgus, 2004, The impact of cyclooxygenase-2 mediated inflammation on scarless fetal wound healing, Am J Pathol, 165, 753, 10.1016/S0002-9440(10)63338-X · DOI
  18. Cowin, 1998, Endogenous inflammatory response to dermal wound healing in the fetal and adult mouse, Dev Dyn, 212, 385, 10.1002/(SICI)1097-0177(199807)212:3<385::AID-AJA6>3.0.CO;2-D · DOI · Paper page
  19. Estes, 1994, Phenotypic and functional features of myofibroblasts in sheep fetal wounds, Differentiation, 56, 173, 10.1046/j.1432-0436.1994.5630173.x · DOI
  20. Martin, 1992, Actin cables and epidermal movement in embryonic wound healing, Nature, 360, 179, 10.1038/360179a0 · DOI
  21. McCluskey, 1995, Analysis of the tissue movements of embryonic wound healing–DiI studies in the limb bud stage mouse embryo, Dev Biol, 170, 102, 10.1006/dbio.1995.1199 · DOI
  22. Whitby, 1991, Immunohistochemical localization of growth factors in fetal wound healing, Dev Biol, 147, 207, 10.1016/S0012-1606(05)80018-1 · DOI
  23. Larson, 2010, Scarless fetal wound healing: A basic science review, Plast Reconstr Surg, 126, 1172, 10.1097/PRS.0b013e3181eae781 · DOI
  24. Merkel, 1988, Type I and type III collagen content of healing wounds in fetal and adult rats, Proc Soc Exp Biol Med, 187, 493, 10.3181/00379727-187-42694 · DOI
  25. Whitby, 1991, The extracellular matrix of lip wounds in fetal, neonatal and adult mice, Development, 112, 651, 10.1242/dev.112.2.651 · DOI
  26. Liechty, 2000, Fetal wound repair results in scar formation in interleukin-10-deficient mice in a syngeneic murine model of scarless fetal wound repair, J Pediatr Surg, 35, 866, 10.1053/jpsu.2000.6868 · DOI
  27. Gordon, 2008, Permissive environment in postnatal wounds induced by adenoviral-mediated overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar formation, Wound Repair Regen, 16, 70, 10.1111/j.1524-475X.2007.00326.x · DOI
  28. Gauglitz, 2011, Hypertrophic scarring and keloids: Pathomechanisms and current and emerging treatment strategies, Mol Med, 17, 113, 10.2119/molmed.2009.00153 · DOI · Paper page
  29. Carey, 2010, Single-gene transgenic mouse strains for reprogramming adult somatic cells, Nat Methods, 7, 56, 10.1038/nmeth.1410 · DOI
  30. Park, 2014, PDGF-BB does not accelerate healing in diabetic mice with splinted skin wounds, PLoS One, 9, e104447, 10.1371/journal.pone.0104447 · DOI
  31. Schmittgen, 2008, Analyzing real-time PCR data by the comparative C(T) method, Nat Protoc, 3, 1101, 10.1038/nprot.2008.73 · DOI · Paper page
  32. Hauck, 2017, Early-stage metastasis requires Mdm2 and not p53 gain of function, Mol Cancer Res, 15, 1598, 10.1158/1541-7786.MCR-17-0174 · DOI
  33. Hebda, 2003, Absence of inhibition of cutaneous wound healing in mice by oral doxycycline, Wound Repair Regen, 11, 373, 10.1046/j.1524-475X.2003.11510.x · DOI
  34. Wang, 2008, Increased severity of bleomycin-induced skin fibrosis in mice with leukocyte-specific protein 1 deficiency, J Invest Dermatol, 128, 2767, 10.1038/jid.2008.164 · DOI
  35. Masur, 1996, Myofibroblasts differentiate from fibroblasts when plated at low density, Proc Natl Acad Sci USA, 93, 4219, 10.1073/pnas.93.9.4219 · DOI
  36. Khorasani, 2011, A quantitative approach to scar analysis, Am J Pathol, 178, 621, 10.1016/j.ajpath.2010.10.019 · DOI
  37. Takahashi, 2007, Induction of pluripotent stem cells from fibroblast cultures, Nat Protoc, 2, 3081, 10.1038/nprot.2007.418 · DOI
  38. Li, 2010, A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts, Cell Stem Cell, 7, 51, 10.1016/j.stem.2010.04.014 · DOI · Paper page
  39. Samavarchi-Tehrani, 2010, Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming, Cell Stem Cell, 7, 64, 10.1016/j.stem.2010.04.015 · DOI · Paper page
  40. Maherali, 2009, Tgfbeta signal inhibition cooperates in the induction of iPSCs and replaces Sox2 and cMyc, Curr Biol, 19, 1718, 10.1016/j.cub.2009.08.025 · DOI · Paper page
  41. Peinado, 2003, Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: Mechanisms for epithelial mesenchymal transitions, J Biol Chem, 278, 21113, 10.1074/jbc.M211304200 · DOI
  42. Shah, 1995, Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous ratwounds reduces scarring, J Cell Sci, 108, 985, 10.1242/jcs.108.3.985 · DOI
  43. Ferguson, 2004, Scar-free healing: From embryonic mechanisms to adult therapeutic intervention, Philos Trans R Soc Lond B Biol Sci, 359, 839, 10.1098/rstb.2004.1475 · DOI · Paper page
  44. Akhurst, 2012, Targeting the TGFβ signalling pathway in disease, Nat Rev Drug Discov, 11, 790, 10.1038/nrd3810 · DOI · Paper page
  45. Shah, 1994, Neutralising antibody to TGF-beta 1,2 reduces cutaneous scarring in adult rodents, J Cell Sci, 107, 1137, 10.1242/jcs.107.5.1137 · DOI
  46. Desmoulière, 1993, Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts, J Cell Biol, 122, 103, 10.1083/jcb.122.1.103 · DOI
  47. Horstmeyer, 2005, Signalling and regulation of collagen I synthesis by ET-1 and TGF-beta1, FEBS J, 272, 6297, 10.1111/j.1742-4658.2005.05016.x · DOI
  48. Ferrari, 2006, VEGF, a prosurvival factor, acts in concert with TGF-β1 to induce endothelial cell apoptosis, Proc Natl Acad Sci USA, 103, 17260, 10.1073/pnas.0605556103 · DOI
  49. Moulin, 2000, Role of wound healing myofibroblasts on re-epithelialization of human skin, Burns, 26, 3, 10.1016/S0305-4179(99)00091-1 · DOI
  50. Kishi, 2012, Fetal skin possesses the ability to regenerate completely: Complete regeneration of skin, Keio J Med, 61, 101, 10.2302/kjm.2011-0002-IR · DOI
  51. Yilmazer, 2013, In vivo cell reprogramming towards pluripotency by virus-free overexpression of defined factors, PLoS One, 8, e54754, 10.1371/journal.pone.0054754 · DOI

Cited by

Sorted by citations

Metadata

Authors
Doeser, M. C., Schöler, H. R., & Wu, G.
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2018-05-25
Volume
36
Issue
8
Pages
1216-1225
ISSN
  • 1066-5099
  • 1549-4918
DOI
10.1002/stem.2842
Cited by
83
References
6
Language
en
Licence
Funders
Max Planck Society

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review