Bone marrow-derived cells contribute to epithelial engraftment during wound healing

Xenia Borue, Sean Lee, Joanna Grove, Erica L. Herzog, Robert Harris, Thomas Diflo, Earl Glusac, Kevin Hyman, Neil D. Theise, Diane S. Krause

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (≤ 1%) in the absence of injury. Here we show that skin damage affects the degree of engraftment of BMDC as keratinocytes and that the keratinocytes are actively cycling. Female mice reconstituted with sex-mismatched BM were wounded by punch biopsy and incision. At the wound site, engraftment of BMDC as epidermal cells increased within 1 day, and continued to increase to approximately 4% by 3 weeks after injury. Using a Cre-lox system, fusion of BMDC with epithelial cells was ruled out. BMDC-derived epithelial cells at the wound edges expressed Ki67, a marker for actively cycling cells, and this proliferation correlated with an increase in the number of donor-derived cells within the wound. Donor-derived cytokeratln 5-expressing cells were rare, suggesting that BMDC do not engraft as epidermal stem cells, and the level of engraftment peaked and then decreased over time, further suggesting that BMDC may assist in early wound healing by engrafting as transit-amplifying cells, which then differentiate into keratinocytes.

Original languageEnglish (US)
Pages (from-to)1767-1772
Number of pages6
JournalAmerican Journal of Pathology
Volume165
Issue number5
DOIs
StatePublished - Jan 1 2004

Fingerprint

Bone Marrow Cells
Wound Healing
Keratinocytes
Wounds and Injuries
Epithelial Cells
Skin
Stem Cells
Bone Marrow
Maintenance
Cell Proliferation
Biopsy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Borue, X., Lee, S., Grove, J., Herzog, E. L., Harris, R., Diflo, T., ... Krause, D. S. (2004). Bone marrow-derived cells contribute to epithelial engraftment during wound healing. American Journal of Pathology, 165(5), 1767-1772. https://doi.org/10.1016/S0002-9440(10)63431-1

Bone marrow-derived cells contribute to epithelial engraftment during wound healing. / Borue, Xenia; Lee, Sean; Grove, Joanna; Herzog, Erica L.; Harris, Robert; Diflo, Thomas; Glusac, Earl; Hyman, Kevin; Theise, Neil D.; Krause, Diane S.

In: American Journal of Pathology, Vol. 165, No. 5, 01.01.2004, p. 1767-1772.

Research output: Contribution to journalArticle

Borue, X, Lee, S, Grove, J, Herzog, EL, Harris, R, Diflo, T, Glusac, E, Hyman, K, Theise, ND & Krause, DS 2004, 'Bone marrow-derived cells contribute to epithelial engraftment during wound healing', American Journal of Pathology, vol. 165, no. 5, pp. 1767-1772. https://doi.org/10.1016/S0002-9440(10)63431-1
Borue, Xenia ; Lee, Sean ; Grove, Joanna ; Herzog, Erica L. ; Harris, Robert ; Diflo, Thomas ; Glusac, Earl ; Hyman, Kevin ; Theise, Neil D. ; Krause, Diane S. / Bone marrow-derived cells contribute to epithelial engraftment during wound healing. In: American Journal of Pathology. 2004 ; Vol. 165, No. 5. pp. 1767-1772.
@article{d138f25a1b944775a13dc61675a3761c,
title = "Bone marrow-derived cells contribute to epithelial engraftment during wound healing",
abstract = "Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (≤ 1{\%}) in the absence of injury. Here we show that skin damage affects the degree of engraftment of BMDC as keratinocytes and that the keratinocytes are actively cycling. Female mice reconstituted with sex-mismatched BM were wounded by punch biopsy and incision. At the wound site, engraftment of BMDC as epidermal cells increased within 1 day, and continued to increase to approximately 4{\%} by 3 weeks after injury. Using a Cre-lox system, fusion of BMDC with epithelial cells was ruled out. BMDC-derived epithelial cells at the wound edges expressed Ki67, a marker for actively cycling cells, and this proliferation correlated with an increase in the number of donor-derived cells within the wound. Donor-derived cytokeratln 5-expressing cells were rare, suggesting that BMDC do not engraft as epidermal stem cells, and the level of engraftment peaked and then decreased over time, further suggesting that BMDC may assist in early wound healing by engrafting as transit-amplifying cells, which then differentiate into keratinocytes.",
author = "Xenia Borue and Sean Lee and Joanna Grove and Herzog, {Erica L.} and Robert Harris and Thomas Diflo and Earl Glusac and Kevin Hyman and Theise, {Neil D.} and Krause, {Diane S.}",
year = "2004",
month = "1",
day = "1",
doi = "10.1016/S0002-9440(10)63431-1",
language = "English (US)",
volume = "165",
pages = "1767--1772",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Bone marrow-derived cells contribute to epithelial engraftment during wound healing

AU - Borue, Xenia

AU - Lee, Sean

AU - Grove, Joanna

AU - Herzog, Erica L.

AU - Harris, Robert

AU - Diflo, Thomas

AU - Glusac, Earl

AU - Hyman, Kevin

AU - Theise, Neil D.

AU - Krause, Diane S.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (≤ 1%) in the absence of injury. Here we show that skin damage affects the degree of engraftment of BMDC as keratinocytes and that the keratinocytes are actively cycling. Female mice reconstituted with sex-mismatched BM were wounded by punch biopsy and incision. At the wound site, engraftment of BMDC as epidermal cells increased within 1 day, and continued to increase to approximately 4% by 3 weeks after injury. Using a Cre-lox system, fusion of BMDC with epithelial cells was ruled out. BMDC-derived epithelial cells at the wound edges expressed Ki67, a marker for actively cycling cells, and this proliferation correlated with an increase in the number of donor-derived cells within the wound. Donor-derived cytokeratln 5-expressing cells were rare, suggesting that BMDC do not engraft as epidermal stem cells, and the level of engraftment peaked and then decreased over time, further suggesting that BMDC may assist in early wound healing by engrafting as transit-amplifying cells, which then differentiate into keratinocytes.

AB - Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (≤ 1%) in the absence of injury. Here we show that skin damage affects the degree of engraftment of BMDC as keratinocytes and that the keratinocytes are actively cycling. Female mice reconstituted with sex-mismatched BM were wounded by punch biopsy and incision. At the wound site, engraftment of BMDC as epidermal cells increased within 1 day, and continued to increase to approximately 4% by 3 weeks after injury. Using a Cre-lox system, fusion of BMDC with epithelial cells was ruled out. BMDC-derived epithelial cells at the wound edges expressed Ki67, a marker for actively cycling cells, and this proliferation correlated with an increase in the number of donor-derived cells within the wound. Donor-derived cytokeratln 5-expressing cells were rare, suggesting that BMDC do not engraft as epidermal stem cells, and the level of engraftment peaked and then decreased over time, further suggesting that BMDC may assist in early wound healing by engrafting as transit-amplifying cells, which then differentiate into keratinocytes.

UR - http://www.scopus.com/inward/record.url?scp=7244221435&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7244221435&partnerID=8YFLogxK

U2 - 10.1016/S0002-9440(10)63431-1

DO - 10.1016/S0002-9440(10)63431-1

M3 - Article

VL - 165

SP - 1767

EP - 1772

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 5

ER -