Donor‐derived myofibroblasts in the ocular surface after allogeneic haematopoietic stem cell transplantation

Hallberg, David; Wernstedt, Pernilla; Hanson, Charles; Wettergren, Yvonne; Stenberg, K; Brüne, Martin; Stenevi, Ulf

doi:10.1111/j.1600-0420.2006.00748.x

Cited by 14 publications

(19 citation statements)

References 24 publications

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“…16 Donor-derived conjunctival epithelia and myofibroblasts have also been detected after sex-mismatched HSCT by staining for the Y chromosome in female allograft recipients. 17,18 However, the proportion of such cells is very small, and their contribution to pathogenic processes remains unknown.…”

Section: Basic Research On Ocular Cgvhdmentioning

confidence: 99%

Immune Processes and Pathogenic Fibrosis in Ocular Chronic Graft-Versus-Host Disease and Clinical Manifestations after Allogeneic Hematopoietic Stem Cell Transplantation

Ogawa

Shimmura

Doğru

et al. 2010

Cornea

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Activation of the immune system and progressive fibrosis are prominent features of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation. The main histologic findings in affected exocrine glands are marked fibrosis of the interstitium and prominent increase in the number of fibroblasts, accompanied by mild lymphocytic infiltration. Clinically, the severity of dry eye is correlated with the degree of fibrotic changes, rather than with the amount of lymphocytic infiltration, indicating that excessive extracellular matrix accumulation primarily contributes to the exocrine dysfunction. We have found that accumulated fibroblasts in the lacrimal gland of patients with cGVHD have a chimeric status. Thus, fibroblasts originating from circulating donor-derived precursors and recipient-derived fibroblasts by local epithelial mesenchymal transition may participate in the excessive fibrosis in patients with cGVHD by interacting with T cells. In this article, the immune response and pathogenic fibrosis in ocular cGVHD will be discussed. In addition, clinical findings of ocular complications after hematopoietic stem cell transplantation and currently available treatment will also be discussed.

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Section: Basic Research On Ocular Cgvhdmentioning

confidence: 99%

Immune Processes and Pathogenic Fibrosis in Ocular Chronic Graft-Versus-Host Disease and Clinical Manifestations after Allogeneic Hematopoietic Stem Cell Transplantation

Ogawa

Shimmura

Doğru

et al. 2010

Cornea

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“…5,10,11 Briefly, samples were thawed and fixed in ethanol:acetic acid (3:1) for 15 min and then allowed to air dry. The membrane was removed from the plastic holder with a sterile scalpel and placed on a glass slide.…”

Section: Fluorescence In Situ Hybridization (Fish)mentioning

confidence: 99%

“…MFBs have been indicated as effector cells in various connective tissue disorders, and MFB dysregulation may cause fibrosis and loss of function. 3 In a previous study, 5 we utilized imprint cytology to extract cells from the ocular surface. We reported the presence of conjunctival donor-derived MFBs in allo-SCT recipients and also the occurrence of giant polyploid (PP) cells of recipient origin.…”

Section: Introductionmentioning

confidence: 99%

Conjunctival polyploid cells and donor-derived myofibroblasts in ocular GvHD

Hallberg

Stenberg

Hanson

et al. 2016

Bone Marrow Transplant

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After allogeneic hematopoietic stem cell transplantation (allo-SCT), ocular GvHD is a common complication, typical symptoms being dry eye syndrome with features of fibrosis. In this study, we have identified and quantified two cell types-myofibroblasts (MFB) and polyploid (PP) cells-in the conjunctival surface of allo-SCT patients (pts) and have explored their kinetics and association with local and systemic GvHD. Results are compared with control groups of (a) pretransplant samples from allo-SCT patients, (b) recipients of autologous transplantation (auto-SCT) and (c) healthy controls. Imprint cytologies were obtained by pressing the conjunctival surface with a sterile, non-abrasive cellulose acetate filter (Millipore). After retraction, typically a monolayer of the outermost cells of the epithelium were retrieved. MFB were identified by immunofluorescent (IF) staining for alpha-smooth muscle protein. PP cells were detected by aberrant chromosome content analyzed via X/Y-FISH (X/Y fluorescence in situ hybridization). In female pts with a male donor (M → F group), donor genotype were identified by sex chromosome detection using FISH methodology. IF and FISH methods were applied in situ on the same filter, and amounts of MFB and PP cells are expressed as the percentage of all cells on the filter. In all, 70 samples from 46 pts were obtained 1-122 months after allo-SCT. The total MFB density (MFB TOT ) was higher in allo-SCT pts compared with healthy individuals and auto-SCT pts and increased by time after transplantation (P o0.001). In M → F recipients, this increase proved to be due to a significant (P o 0.001) and gradual elevation of donor-derived MFB (MFB XY ), whereas recipient-derived MFB (MFB XX ) did not vary over time. Clinical ocular GvHD correlated with MFB XY /MFB TOT ratio (P = 0.034), whereas no association between MFB TOT or MFB XY systemic GvHD was observed. In the M → F group (n = 25), both MFB XY and MFB XX were detected on 28 of the 37 imprints (76%). In pts 436 months post transplant, on 11/12 imprints, a median of 9.4% (1.4-39%) MFB XY and 3.6% (0-11%) MFB XX was found. In one patient, 1.6% MFB XY were detected at 3 weeks post transplant. PP cells (6-24n), exclusively of recipient origin, were found to a median of 0.6% (0-37%). The PP cell density differed significantly (P o0.001) between time intervals, with a maximum 8.9% (0-35%) of all cells at 3-12 months. No correlation between PP cells and GvHD (ocular or systemic) was observed. The MFB has been indicated as a culprit in chronic inflammation and fibrosis. The observation that MFB XY /MFB TOT ratio correlated with ocular GvHD suggests a role of donor MFB in GvHD pathogenesis. The constant finding of recipient-derived MFB XX cells many years after transplant in pts with 100% donor hematopoiesis indicates that there is a non-hematopoietic differentiation route to MFB. The origin and role of PP cells after allo-SCT remains obscure.

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“…Our next aim seems be a reduction of the serious eye injuries among children caused by airsoft gun pellets. n a recent study (Hallberg et al 2006), our group reported the presence of donor-derived cells in the ocular surfaces of recipients of allogeneic bone marrow transplantation (allo-BMT). These cells were found to be myofibroblasts, i.e.…”

mentioning

confidence: 99%