Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts

C. C. Compton, S. Regauer, G. R. Seiler, D. B. Landry

Research output: Contribution to journalArticle

Abstract

Human Merkel cell regeneration in epidermis derived from cultured keratinocyte autografts was studied from 6 days to 6 years after transplantation. Cultured keratinocyte sheets derived from skin of the sole, axilla, groin, or scalp were transplanted to full-thickness wounds in 20 pediatric patients treated for massive burns or giant congenital nevi. Normal age- and site-matched skin as well as meshed split-thickness autografts from the same patients served as controls. Merkel cells were identified by immunohistochemistry using antibodies to cytokeratins paragraph 8 and paragraph 18. Cultured keratinocytes in vitro expressed no neuroendocrine markers, but nonspecific, simple-epithelial cytokeratin expression was observed in about 20% of cells. After transplantation, Merkel cells were identified only in cultured grafts derived from sole skin and appeared in the epidermis as early as 21 days postgrafting. Dermal Merkel cells were rarely observed, but their appearance invariably succeeded that of intraepidermal Merkel cells. Regenerated Merkel cells were never innervated, and their emergence was unrelated either spatially or temporally to epidermal reinnervation. In skin bridges of meshed split-thickness grafts, Merkel cells survived after degeneration of associated neurites, but no Merkel cells appeared within re-epithelialized interstices. Among the neuroendocrine markers tested, Merkel cells in cultured grafts, meshed skin grafts or normal pediatric skin expressed only neuron-specific enolase. They failed to stain for calcitonin, chromogranin A, Leu-7, synaptophysin, bombesin, or vasoactive intestinal polypeptide by immunohistochemistry. These findings suggest that: (a) Merkel cells derive from keratinocyte precursors which undergo neuroendocrine differentiation in the epidermis; (b) that keratinocyte stem cells are capable of undergoing Merkel cell differentiation postnatally; (c) that postnatal Merkel cell differentiation may be body-site dependent; and (d) that Merkel cell development and maintenance is independent of neural induction.

Original languageEnglish (US)
Pages (from-to)233-241
Number of pages9
JournalLaboratory Investigation
Volume63
Issue number2
StatePublished - 1990
Externally publishedYes

Fingerprint

Merkel Cells
Keratinocytes
Regeneration
Transplants
Skin
Epidermis
Autografts
Cell Differentiation
Transplantation
Immunohistochemistry
Keratin-8
Pediatrics
Chromogranin A
Bombesin
Synaptophysin
Axilla
Phosphopyruvate Hydratase
Groin
Nevus
Vasoactive Intestinal Peptide

Keywords

  • cultured autografts
  • meshed split-thickness grafts
  • neuroendocrine differentiation
  • site-specificity
  • skin regeneration

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Compton, C. C., Regauer, S., Seiler, G. R., & Landry, D. B. (1990). Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts. Laboratory Investigation, 63(2), 233-241.

Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts. / Compton, C. C.; Regauer, S.; Seiler, G. R.; Landry, D. B.

In: Laboratory Investigation, Vol. 63, No. 2, 1990, p. 233-241.

Research output: Contribution to journalArticle

Compton, CC, Regauer, S, Seiler, GR & Landry, DB 1990, 'Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts', Laboratory Investigation, vol. 63, no. 2, pp. 233-241.
Compton, C. C. ; Regauer, S. ; Seiler, G. R. ; Landry, D. B. / Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts. In: Laboratory Investigation. 1990 ; Vol. 63, No. 2. pp. 233-241.
@article{dee9f61293ff4cd39bfcccb3f391b6cc,
title = "Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts",
abstract = "Human Merkel cell regeneration in epidermis derived from cultured keratinocyte autografts was studied from 6 days to 6 years after transplantation. Cultured keratinocyte sheets derived from skin of the sole, axilla, groin, or scalp were transplanted to full-thickness wounds in 20 pediatric patients treated for massive burns or giant congenital nevi. Normal age- and site-matched skin as well as meshed split-thickness autografts from the same patients served as controls. Merkel cells were identified by immunohistochemistry using antibodies to cytokeratins paragraph 8 and paragraph 18. Cultured keratinocytes in vitro expressed no neuroendocrine markers, but nonspecific, simple-epithelial cytokeratin expression was observed in about 20{\%} of cells. After transplantation, Merkel cells were identified only in cultured grafts derived from sole skin and appeared in the epidermis as early as 21 days postgrafting. Dermal Merkel cells were rarely observed, but their appearance invariably succeeded that of intraepidermal Merkel cells. Regenerated Merkel cells were never innervated, and their emergence was unrelated either spatially or temporally to epidermal reinnervation. In skin bridges of meshed split-thickness grafts, Merkel cells survived after degeneration of associated neurites, but no Merkel cells appeared within re-epithelialized interstices. Among the neuroendocrine markers tested, Merkel cells in cultured grafts, meshed skin grafts or normal pediatric skin expressed only neuron-specific enolase. They failed to stain for calcitonin, chromogranin A, Leu-7, synaptophysin, bombesin, or vasoactive intestinal polypeptide by immunohistochemistry. These findings suggest that: (a) Merkel cells derive from keratinocyte precursors which undergo neuroendocrine differentiation in the epidermis; (b) that keratinocyte stem cells are capable of undergoing Merkel cell differentiation postnatally; (c) that postnatal Merkel cell differentiation may be body-site dependent; and (d) that Merkel cell development and maintenance is independent of neural induction.",
keywords = "cultured autografts, meshed split-thickness grafts, neuroendocrine differentiation, site-specificity, skin regeneration",
author = "Compton, {C. C.} and S. Regauer and Seiler, {G. R.} and Landry, {D. B.}",
year = "1990",
language = "English (US)",
volume = "63",
pages = "233--241",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts

AU - Compton, C. C.

AU - Regauer, S.

AU - Seiler, G. R.

AU - Landry, D. B.

PY - 1990

Y1 - 1990

N2 - Human Merkel cell regeneration in epidermis derived from cultured keratinocyte autografts was studied from 6 days to 6 years after transplantation. Cultured keratinocyte sheets derived from skin of the sole, axilla, groin, or scalp were transplanted to full-thickness wounds in 20 pediatric patients treated for massive burns or giant congenital nevi. Normal age- and site-matched skin as well as meshed split-thickness autografts from the same patients served as controls. Merkel cells were identified by immunohistochemistry using antibodies to cytokeratins paragraph 8 and paragraph 18. Cultured keratinocytes in vitro expressed no neuroendocrine markers, but nonspecific, simple-epithelial cytokeratin expression was observed in about 20% of cells. After transplantation, Merkel cells were identified only in cultured grafts derived from sole skin and appeared in the epidermis as early as 21 days postgrafting. Dermal Merkel cells were rarely observed, but their appearance invariably succeeded that of intraepidermal Merkel cells. Regenerated Merkel cells were never innervated, and their emergence was unrelated either spatially or temporally to epidermal reinnervation. In skin bridges of meshed split-thickness grafts, Merkel cells survived after degeneration of associated neurites, but no Merkel cells appeared within re-epithelialized interstices. Among the neuroendocrine markers tested, Merkel cells in cultured grafts, meshed skin grafts or normal pediatric skin expressed only neuron-specific enolase. They failed to stain for calcitonin, chromogranin A, Leu-7, synaptophysin, bombesin, or vasoactive intestinal polypeptide by immunohistochemistry. These findings suggest that: (a) Merkel cells derive from keratinocyte precursors which undergo neuroendocrine differentiation in the epidermis; (b) that keratinocyte stem cells are capable of undergoing Merkel cell differentiation postnatally; (c) that postnatal Merkel cell differentiation may be body-site dependent; and (d) that Merkel cell development and maintenance is independent of neural induction.

AB - Human Merkel cell regeneration in epidermis derived from cultured keratinocyte autografts was studied from 6 days to 6 years after transplantation. Cultured keratinocyte sheets derived from skin of the sole, axilla, groin, or scalp were transplanted to full-thickness wounds in 20 pediatric patients treated for massive burns or giant congenital nevi. Normal age- and site-matched skin as well as meshed split-thickness autografts from the same patients served as controls. Merkel cells were identified by immunohistochemistry using antibodies to cytokeratins paragraph 8 and paragraph 18. Cultured keratinocytes in vitro expressed no neuroendocrine markers, but nonspecific, simple-epithelial cytokeratin expression was observed in about 20% of cells. After transplantation, Merkel cells were identified only in cultured grafts derived from sole skin and appeared in the epidermis as early as 21 days postgrafting. Dermal Merkel cells were rarely observed, but their appearance invariably succeeded that of intraepidermal Merkel cells. Regenerated Merkel cells were never innervated, and their emergence was unrelated either spatially or temporally to epidermal reinnervation. In skin bridges of meshed split-thickness grafts, Merkel cells survived after degeneration of associated neurites, but no Merkel cells appeared within re-epithelialized interstices. Among the neuroendocrine markers tested, Merkel cells in cultured grafts, meshed skin grafts or normal pediatric skin expressed only neuron-specific enolase. They failed to stain for calcitonin, chromogranin A, Leu-7, synaptophysin, bombesin, or vasoactive intestinal polypeptide by immunohistochemistry. These findings suggest that: (a) Merkel cells derive from keratinocyte precursors which undergo neuroendocrine differentiation in the epidermis; (b) that keratinocyte stem cells are capable of undergoing Merkel cell differentiation postnatally; (c) that postnatal Merkel cell differentiation may be body-site dependent; and (d) that Merkel cell development and maintenance is independent of neural induction.

KW - cultured autografts

KW - meshed split-thickness grafts

KW - neuroendocrine differentiation

KW - site-specificity

KW - skin regeneration

UR - http://www.scopus.com/inward/record.url?scp=0025160927&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025160927&partnerID=8YFLogxK

M3 - Article

C2 - 1696332

AN - SCOPUS:0025160927

VL - 63

SP - 233

EP - 241

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 2

ER -