Absence of donor-derived keratinocyte stem cells in skin tissues cultured from patients after mobilized peripheral blood hematopoietic stem cell transplantation

Hematti, Peiman; Sloand, Elaine M.; Carvallo, Cristián; Albert, Michael R.; Yee, Carole; Fuehrer, Monika; Blancato, Jan; Kearns, W.G.; Barrett, John; Childs, Richard W.; Vogel, Jonathan; Dunbar, Cynthia E.

doi:10.1016/s0301-472x(02)00873-1

Cited by 43 publications

(17 citation statements)

References 33 publications

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“…These findings can be viewed in at least 2 ways: Either the donor-derived keratinocytes require different culture conditions than those used or the donor-derived stem cells became keratinocytes without passing through an intervening tissue-specific stem cell (self-renewing) state. 86 These data may be analogous to those showing engraftment of type 1 but not type 2 pneumocytes, which are functional alveolar stem cells.…”

Section: Bone Marrow To Skinsupporting

confidence: 61%

“…32,53,86 In the human studies, donor-derived keratinocytes were cytokeratin positive and CD45 Ϫ . 53 However, even though 4% to 14% of keratinocytes in human skin were Yϩ, keratinocytes grown in vitro from the same skin biopsies failed to demonstrate any Yϩ donor cells even when sensitive PCR analysis for sequences specific to the Y chromosome was used.…”

Section: Bone Marrow To Skinmentioning

confidence: 99%

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Plasticity of marrow-derived stem cells

Herzog

Chai

Krause

2003

Blood

701

442

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Section: Bone Marrow To Skinsupporting

confidence: 61%

Section: Bone Marrow To Skinmentioning

confidence: 99%

Plasticity of marrow-derived stem cells

Herzog

Chai

Krause

2003

Blood

701

442

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“…Although BM-derived cells have been identified in the skin after hematopoietic cell transplantation (HCT) [11,12], the more important questions are: in which venues do lymphohematopoietic cells substantially contribute to wound healing and how robust must such hematogenous engraftment be to meaningfully contribute to skin function in disease and injury [4,13,14]? Recently, we and others have obtained unexpected insights from animal experimentation [15][16][17] and from our clinical trial of HCT in a prototypic extracellular matrix disorder, epidermolysis bullosa (EB) [18].…”

Section: Introductionmentioning

confidence: 99%

Concise Review: Transplantation of Human Hematopoietic Cells for Extracellular Matrix Protein Deficiency in Epidermolysis Bullosa

2011

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The skin is constantly exposed to environmental insults and requires effective repair processes to maintain its protective function. Wound healing is severely compromised in people with congenital absence of structural proteins of the skin, such as in dystrophic epidermolysis bullosa, a severe congenital mechanobullous disorder caused by mutations in collagen type VII. Remarkably, stem cell transplantation can ameliorate deficiency of this skin-specific structural protein in both animal models and in children with the disorder. Healthy donor cells from the hematopoietic graft migrate to the injured skin; simultaneously, there is an increase in the production of collagen type VII, increased skin integrity, and reduced tendency to blister formation. How hematogenous stem cells from bone marrow and cord blood can alter skin architecture and wound healing in a robust, clinically meaningful way is unclear. We review the data and the resulting hypotheses that have a potential to illuminate the mechanisms for these effects. Further modifications in the use of stem cell transplantation as a durable source of extracellular matrix proteins may make this regenerative medicine approach effective in other cutaneous and extracutaneous conditions. STEM CELLS 2011;29:900-906Disclosure of potential conflicts of interest is found at the end of this article.

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“…In skin, studies have shown that BM provides fibroblast-like cells in the dermis (of hematopoietic and mesenchymal lineages) and that the number of these cells increases after skin wounding (3,4). BM can also generate epithelial cells, i.e., keratinocytes, in the epithelia, although the precise derivations and mechanisms to raise BM-derived keratinocytes are not fully known (3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Human/mouse studies involving transplantation of sex-mismatched or genetically tagged BM cells have shown that keratin-positive bone marrow-derived cells can be found in skin epidermis, hair follicles, and sebaceous glands (6,8,9,11,12,14,16), sites that harbor skin stem cell niches (17).…”

mentioning

confidence: 99%

PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia

Tamai

Yamazaki

Chino

et al. 2011

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

218

201

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The role of bone marrow cells in repairing ectodermal tissue, such as skin epidermis, is not clear. To explore this process further, this study examined a particular form of cutaneous repair, skin grafting. Grafting of full thickness wild-type mouse skin onto mice that had received a green fluorescent protein-bone marrow transplant after whole body irradiation led to an abundance of bone marrow-derived epithelial cells in follicular and interfollicular epidermis that persisted for at least 5 mo. The source of the epithelial progenitors was the nonhematopoietic, platelet-derived growth factor receptor α-positive (Lin − /PDGFRα + ) bone marrow cell population. Skin grafts release high mobility group box 1 (HMGB1) in vitro and in vivo, which can mobilize the Lin − /PDGFRα + cells from bone marrow to target the engrafted skin. These data provide unique insight into how skin grafts facilitate tissue repair and identify strategies germane to regenerative medicine for skin and, perhaps, other ectodermal defects or diseases.

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Absence of donor-derived keratinocyte stem cells in skin tissues cultured from patients after mobilized peripheral blood hematopoietic stem cell transplantation

Cited by 43 publications

References 33 publications

Plasticity of marrow-derived stem cells

Plasticity of marrow-derived stem cells

Concise Review: Transplantation of Human Hematopoietic Cells for Extracellular Matrix Protein Deficiency in Epidermolysis Bullosa

PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia

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