Mesenchymal Stem Cells Can Affect Solid Organ Allograft Survival
ABSTRACT It has recently been recognized that mesenchymal stem cells (MSCs) isolated from adult bone marrow are able to modify the alloimmune response in vitro and in vivo. MSCs can be expanded into large quantities in culture, thereby facilitating potential future applications in solid organ transplantation. To develop novel MSC-based antirejection treatments, the mechanism behind the immunomodulatory ability of MSCs has to be elucidated further. At present, a variety of possible in vitro effects of MSCs on immune system effector cells have been reported, but little is known about their in vivo properties. Here, we discuss recent findings regarding the influence of MSCs on different effector cell populations in vitro and summarize the available data describing their in vivo properties.
SourceAvailable from: Mohamed Zeriouh[Show abstract] [Hide abstract]
ABSTRACT: Purpose To expand the limited donor pool, lung retrieval from non-heart-beating donors (NHBD) was introduced clinically. However, primary graft dysfunction with surfactant inactivation due to I/R-injury is a major cause of early mortality. Furthermore, donor-derived mesenchymal stem cell (MSC) expansion and fibrotic differentiation in the allograft results in deleterious bronchiolitis obliterans syndrome (BOS). Therefore, pretreatment of NHBD with recipient-specific bone-marrow-(BM)-derived MSC might improve postischemic surfactant function and reduce incidence of BOS by numerous parakrine, immunomodulating and tissue-remodeling properties especially on type-II-pneumocytes. Methods and Materials Asystolic pigs (n=5/group) were ventilated for 3h of warm ischemia (groups 1-3). 50x106 BM-MSC, each, were administered in pulmonary artery (group 2) or nebulized endobronchially (group 3) prior to preservation. After left-lung-transplantation grafts were reperfused for 4h. Hemodynamics (PVR), pO2/FiO2 and dynamic compliance (DLC) were compared to lungs without pretreatment (group 1) and sham-controls (Sham). To prove and localize the Texas-red labelled MSCs in the lung, PCR was performed and cryosections were counter-stained with WGA and DAPI. Intra-alveolar edema was determined sterologically. Statistics comprised ANOVA with repeated measurements. Results PVR and DLC were superior in endobronchially pretreated MSC lungs as compared to endovascular MSC application and lungs without pretreatment. Oxygenation was worst after endovascular pretreatment. Stereology revealed low intrapulmonary edema in all groups (p>0.05), successful MSC application was proven by PCR. MSC were localized in alveola and capillaries. Conclusions Intrapulmonary deposition of BM-MSC in NHBD is feasible, but only endobronchial application optimizes DLC and PVR postoperatively. Due to immunomodulatory and paracrine effects on epithelial restitution, autologous-BM-MSC-based donor pretreatment for prevention or attenuation of limiting BOS is very promising in LTx.Journal of Cardiothoracic Surgery 09/2014; 32(4):S15–S16. DOI:10.1016/j.healun.2013.01.019 · 3.05 Impact Factor
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ABSTRACT: Background Donor specific hematopoietic cell transplantation has long been recognized for its potential in tolerance induction for subsequently transplanted organs. We have recently published that co-administration of Myeloid Progenitor (MP) and third party Hematopoietic Stem Cells (HSC) can induce MP-specific tolerance for subsequently transplanted organs . Methods Mice received an allogeneic HSC and third party MP transplantation simultaneous with placement of a MP-matched skin graft. Variants tested include time of graft placement, MP genotype and source of cells. Results Using B10;B6-Rag2−/−Il2rg−/− mice, we demonstrate that specific tolerance can be induced by MP given simultaneous with the skin graft in the complete absence of MP-donor-matched lymphoid cells. Ex vivo expanded MP function as well as sorted cells in inducing tolerance. In addition we demonstrate that tolerance can be induced by MP in the context of autologous HSC transplantation. Conclusions Our results demonstrate that the previously observed expansion of organ donor matched Treg is not essential for tolerance, and that MP tolerance protocols can be envisioned in most clinical settings, including those involving deceased donor organs.Transplant Immunology 08/2014; DOI:10.1016/j.trim.2014.04.001 · 1.83 Impact Factor
Urology 09/2011; 78(3). DOI:10.1016/j.urology.2011.07.535 · 2.13 Impact Factor