Transplantation studies on sheets of pure epidermal epithelium and on epidermal cell suspensions

Billingham, R. E.; Reynolds, Joyce

doi:10.1016/s0007-1226(52)80004-9

Cited by 200 publications

(42 citation statements)

References 9 publications

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“…Neither was seeding with fibroblasts required. Furthermore, studies of skin wounds under the same experimental conditions as above showed that treatment of the wounds with a large variety of growth factors (Greenhalgh et al 1990;Puolakkainen et al 1995) or epidermal cell suspensions or epidermal cell sheets (Billingham & Reynolds 1952;Carver et al 1993), or with a number of scaffolds based on synthetic polymers (Cooper et al 1991;Hansbrough et al 1993), failed to induce dermis regeneration. These and related observations (for review see Yannas 2001) motivate study of the mechanism, discussed below, by which DRT induces stroma regeneration.…”

Section: Regeneration Of Skinmentioning

confidence: 95%

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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Section: Regeneration Of Skinmentioning

confidence: 95%

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

Yannas

2005

J. R. Soc. Interface.

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“…The cultured epithelium is not likely to contain pigment cells or Merkel cells or to re-form hair follicles or sweat glands. Pure epidermal grafts are thought to be less durable than those containing dermis (37). In spite of these shortcomings, the large amount of autologous epithelium that could be made available suggests applications to the therapy of burns, for which large amounts of epidermis may be required.…”

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confidence: 99%

Growth of cultured human epidermal cells into multiple epithelia suitable for grafting.

Green¹,

Kehinde²,

Thomas³

1979

Proc. Natl. Acad. Sci. U.S.A.

1,109

506

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Owing to several recent developments, the cultivability of epidermal keratinocytes, particularly those of the human, has been greatly improved. Under the conditions used, single cultured cells generate stratified colonies that ultimately fuse and form an epithelium that is a reasonable approximation of the epidermis. It will be shown here that large amounts of cultured epithelium can be generated from a small piece of epidermis in a short time. We wish to bring to the attention of surgeons and cell biologists the possibility of using culture-gown epithelium derived from the same individual to restore defects in the epidermis.General description of behavior of cultured human epidermal cells There have been many studies of the epidermis in culture (for review of early work, see ref. 1). Most studies were carried out on explanted fragments, a form of cultivation in which multiplication is usually limited. Although there were difficulties in expanding an epidermal cell population in this way and there was no effective means of controlling fibroblast proliferation, such cultures were shown to be transplantable onto animals by Medawar (2) and Karasek (3), and hopes were expressed very early for application to human transplantation (4, 5). Methods of expanding the size of an epidermal cell population by growth from tissue fragments have since been improved by Freeman et al. (6,7); the proliferated epithelium remained transplantable (8).When the superiority of disaggregated cell culture for obtaining increased proliferation of other cell types was recognized, attempts were made to grow epidermal cells in this way by Prunieras et al. (9) (13), and Marcelo et al. (14). Some multiplication took place in such cultures, but the cells generally were not serially cultivable, either because of overgrowth of fibroblasts or possibly because the epidermal cells when pure were deprived of fibroblast support. In such systems the inoculation density was high, and separated single cells were probably not able to give rise to colonies efficiently.In studies of a keratinocyte line of teratomal origin by Rheinwald and Green (15), it was discovered that the cells could be cultivated serially from small inocula by supporting them with cocultivated lethally irradiated 3T3 cells or other fibroblasts. It was then found (16) that human epidermal cells could be serially cultivated under the same conditions. The following points were established.(i) By use of supporting 3T3 cells, epidermal cells of newborn infants can be serially transferred through numerous subcultures.(ii) Each colony initiated by a single cell forms a stratified squamous epithelium. The basal cells (those attached to the surface of the culture vessel) resemble basal cells of the epidermis in that they account for all cell multiplication, whereas the cells that leave the basal layer become terminally differentiated.(iii) Living fibroblasts, which were present in the original tissue and whose multiplication in culture was formerly uncontrollable, can be controlled by ...

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“…Transplantations of cell dispersions containing epidermocytes without a fibrin matrix have been performed previously without much success [2]. Hunyadi et al [8] were able to heal venous ulcers with non-cultured cell suspensions in fibrin glue, whereas the administration without fibrin glue was without effect [17].…”

Section: Discussionmentioning

confidence: 99%

Cultured autologous keratinocytes suspended in fibrin glue (KFGS) with allogenic overgraft for definitive burn wound coverage

et al. 1995

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In a patient with burns of 88% TBSA autologous cultured keratinocyte fibrin glue suspension (KFGS) overgrafted with fresh split thickness allogenic skin was used as definitive wound coverage after epifascial debridement and temporary allogenic closure. A total of 22% TBSA were closed in this way including a complete leg except the foot. For comparison, the contralateral leg was covered with conventional autologous sheet grafts (CEA). Histology revealed a layered squamous epithelium, and evidence of at least partial integration of allogenic dermis including the formation of a well-organized rete structure even after deep necretomy. Besides the rapid stable closure and good skin quality, the new technique has the advantages of early availability, simple handling, easy repetition, and the transfer of actively proliferating epidermal cells. This is the first case proving that KFGS with allogenic overgrafts leads to permanent epithelialization of large epifascial wounds. The technique compared favorably with CEA with regard to availability, handling, and stability.

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Transplantation studies on sheets of pure epidermal epithelium and on epidermal cell suspensions

Cited by 200 publications

References 9 publications

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

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

Growth of cultured human epidermal cells into multiple epithelia suitable for grafting.

Cultured autologous keratinocytes suspended in fibrin glue (KFGS) with allogenic overgraft for definitive burn wound coverage

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