Restoration of Erythropoiesis by Rituximab in an Adult Patient with Primary Acquired Pure Red Cell Aplasia Refractory to Conventional Treatment

British Journal of Haematology. Mar, 2002  |  Pubmed ID: 11879264

Dendritic Cell Deficiency in Early B Cell Chronic Lymphocytic Leukemia

Haematologica. Jan, 2004  |  Pubmed ID: 14754617

Neutrophilic Leukemoid Reaction As the Presenting Feature of De Novo and Therapy-related Acute Leukemias

Acta Haematologica. 2004  |  Pubmed ID: 15153719

Sunburn Cell Formation, Dendritic Cell Migration, and Immunomodulatory Factor Production After Solar-simulated Irradiation of Sunscreen-treated Human Skin Explants in Vitro

The Journal of Investigative Dermatology. Oct, 2004  |  Pubmed ID: 15373785

Using human skin explants, we investigated the effects of two different sunscreen preparations containing a chemical UVB filter alone [sun protection factor (SPF) 5.2] or UVA+UVB filter [SPF 6.2] on sunburn cell formation, dendritic cell (DC) migration, CD86- and CD1a-positive cell number, and tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-1, IL-10, and IL-12 production in the skin after irradiation with different doses of solar-simulated UV radiation. Sunscreen- or placebo-treated skin explants were irradiated with solar-simulated UV radiation at 0.5, 1, and 2 minimal erythematous dose equivalents (MEDE) (as determined in an in vivo human study) multiplied by the SPF of the placebo or sunscreens. After irradiation, skin explants were floated on RMPI medium for 48 h. Cells that had emigrated and the skin explants were histologically analyzed, and the soluble mediators were measured in the supernatants by ELISA. Exposure to UV radiation led to concentration-dependent increases in sunburn cell formation and TNFalpha production but a concentration-dependent decrease in DC migration and CD86- and CD1a-positive cell number in the epidermis. Both chemical sunscreens protected against those alterations. The immunoprotective capacity of the sunscreens correlated with their SPF but was independent of the sunscreens' UVA protection capacity, suggesting that UVA is not a major factor for immunosuppression under the conditions used in the model. UV irradiation did not significantly affect the vitality of emigrated DC; the expression of HLA, CD80, and lag on emigrated cells; the number of CD1a-positive cells in the dermis; or the production of IL-1, IL-10, and IL-12. We conclude that our model may be useful in determining the immunoprotective capacity of sunscreens.

Phenotypic Characterization and Preclinical Production of Human Lineage-negative Cells for Regenerative Stem Cell Therapy

Transfusion. Mar, 2005  |  Pubmed ID: 15752148

Regenerative stem cell therapy (SCT) is currently being tested in clinical trials. The ideal type and source of cells have not yet been defined. Lineage (Lin) depletion is an experimental procedure capable of enriching all recently recognized SC types with regenerative potency. This study was performed to define a practicable monoclonal antibody (MoAb) cocktail for Lin depletion and to test whether clinical-scale Lin depletion is possible.

Blood Monocytes Mimic Endothelial Progenitor Cells

Stem Cells (Dayton, Ohio). Feb, 2006  |  Pubmed ID: 16141361

The generation of endothelial progenitor cells (EPCs) from blood monocytes has been propagated as a novel approach in the diagnosis and treatment of cardiovascular diseases. Low-density lipoprotein (LDL) uptake and lectin binding together with endothelial marker expression are commonly used to define these EPCs. Considerable controversy exists regarding their nature, in particular, because myelomonocytic cells share several properties with endothelial cells (ECs). This study was performed to elucidate whether the commonly used endothelial marker determination is sufficient to distinguish supposed EPCs from monocytes. We measured endothelial, hematopoietic, and progenitor cell marker expression of monocytes before and after angiogenic culture by fluorescence microscopy, flow cytometry, and real-time reverse transcription-polymerase chain reaction. The function of primary monocytes and monocyte-derived supposed EPCs was investigated during vascular network formation and EC colony-forming unit (CFU-EC) development. Monocytes cultured for 4 to 6 days under angiogenic conditions lost CD14/CD45 and displayed a commonly accepted EPC phenotype, including LDL uptake and lectin binding, CD31/CD105/CD144 reactivity, and formation of cord-like structures. Strikingly, primary monocytes already expressed most tested endothelial genes and proteins at even higher levels than their supposed EPC progeny. Neither fresh nor cultured monocytes formed vascular networks, but CFU-EC formation was strictly dependent on monocyte presence. LDL uptake, lectin binding, and CD31/CD105/CD144 expression are inherent features of monocytes, making them phenotypically indistinguishable from putative EPCs. Consequently, monocytes and their progeny can phenotypically mimic EPCs in various experimental models.

CD45-positive Cells of Haematopoietic Origin Enhance Chondrogenic Marker Gene Expression in Rat Marrow Stromal Cells

International Journal of Molecular Medicine. Aug, 2006  |  Pubmed ID: 16820929

Adult mesenchymal stem cells (MSCs) can be readily isolated from bone marrow, expanded in culture and subsequently subjected to differentiation into various connective tissue lineages. In general, for animal studies separation of MSCs from other bone marrow-derived cells is achieved by sole adherence to plastic surface of tissue culture flasks; however, this procedure produces a heterogeneous cell population containing CD45-positive haematopoietic cells (HCs) and haematopoietic stem cells (HSCs). It is known, that mixed cell cultures consisting of cocultures of differentiated somatic cells with adult stem cells promote differentiation towards specific cell lineages. For determining the effect of the CD45-positive cell population on the differentiation potential of MSCs, we sorted out the bone marrow-derived adherent cells by immunomagnetic technique (MACS) to attain a subpopulation of CD45-depleted cells. Herein, we show that the presence of adherent CD45-positive HCs not only promote expression of the chondrogenic marker genes Col2a1, COMP and Sox9, but also of Col1a1, Col10a1 and to a certain degree Cbfa1 in MSCs when cultured in an appropriate three-dimensional environment. These observations constitute a step towards unravelling the influence of haematopoietic cells on chondrogenic differentiation of MSCs.

Stem Cell Therapy for Ischemic Heart Disease: Beginning or End of the Road?

Cell Transplantation. 2006  |  Pubmed ID: 16826795

Despite improvements in emergency treatment, myocardial infarction is often the beginning of a downward spiral leading to congestive heart failure. Other than heart transplantation, current therapeutic means aim at enabling the organism to survive with a heart that is working at a fraction of its original capacity. It is therefore no surprise that cardiac stem cell therapy has raised many hopes. However, neither the ideal source and type of stem cell nor the critical cell number and mode of application have been defined so far. Early reports on myocardial repair by adult bone marrow stem cells from rodent models promoted an unparalleled boost of clinical and experimental cell therapy studies. The phenomenon of stem/progenitor cell-induced angiogenesis in ischemic myocardium has ever since been reproduced by numerous groups in a variety of small and large animal models. Myogenesis, however, is an altogether different matter. Many of the initial clinical studies were fueled by the suggestion that early hematopoietic stem cells have a plasticity high enough to enable cross-lineage differentiation into cells of cardiomyocyte phenotype, but the initial enthusiasm has largely faded. The myogenic potential of stroma cell-derived mesenchymal stem cells is much better documented in animal models, but transfer to the clinical setting faces a variety of obstacles. In clinical pilot trials, we and others have demonstrated the feasibility and safety of administering progenitor cells derived from autologous bone marrow to the myocardium of patients with ischemic heart disease. Clinical efficacy data are still rare, but the few controlled trials that have been completed uniformly show a tendency towards better heart function in cell-treated patients. This review is an attempt to describe the scientific basis for cardiac cell therapy from the point of view of the clinician, focusing on problems that arise with beginning translation into the clinical setting.

Immune Cells Mimic the Morphology of Endothelial Progenitor Colonies in Vitro

Stem Cells (Dayton, Ohio). Jul, 2007  |  Pubmed ID: 17395771

Endothelial progenitor cells (EPC) are considered powerful biologic markers for vascular function and cardiovascular risk, predicting events and death from cardiovascular causes. Colony-forming units of endothelial progenitor cells (CFU-EC) are used to quantify EPC circulating in human peripheral blood. The mechanisms underlying colony formation and the nature of the contributing cells are not clear. We performed subtractive CFU-EC analyses to determine the impact of various blood cell types and kinetics of protein and gene expression during colony formation. We found that CFU-EC mainly comprise T cells and monocytes admixed with B cells and natural killer cells. The combination of purified T cells and monocytes formed CFU-EC structures. The lack of colonies after depletion or functional ablation of T cells or monocytes was contrasted with effective CFU-EC formation in the absence of CD34+ cells. Microarray analyses revealed activation of immune function-related biological processes without changes in angiogenesis-related processes during colony formation. In concordance with a regenerative function, soluble factors derived from CFU-EC cultures supported vascular network formation in vitro. Recognizing CFU-EC formation as the result of a functional cross between T cells and monocytes shifts expectations of vascular regenerative medicine. Our data support the move from a view of circulating EPC toward models that include a role for immune cells in vascular regeneration. Disclosure of potential conflicts of interest is found at the end of this article.

Humanized System to Propagate Cord Blood-derived Multipotent Mesenchymal Stromal Cells for Clinical Application

Regenerative Medicine. Jul, 2007  |  Pubmed ID: 17635045

Umbilical cord blood (UCB) is an easily accessible alternative source for multipotent mesenchymal stromal cells (MSCs) and is generally believed to provide MSCs with a higher proliferative potential compared with adult bone marrow. Limitations in cell number and strict dependence of expansion procedures from selected lots of fetal bovine serum have hampered the progress of clinical applications with UCB-derived MSCs.

Two Steps to Functional Mesenchymal Stromal Cells for Clinical Application

Transfusion. Aug, 2007  |  Pubmed ID: 17655587

Ex vivo expansion of multipotent mesenchymal stromal cells (MSCs) is a prerequisite for evaluating their therapeutic potential in ongoing clinical trials. Even large volumes of starting material and extended culture periods, however, do not necessarily produce 2 x 10(6) MSCs per kg per adult patient. A new two-step procedure has been devised to propagate more than 1 x 10(8) MSCs from small marrow volumes within fewer than 4 weeks.

Human Platelet Lysate Can Replace Fetal Bovine Serum for Clinical-scale Expansion of Functional Mesenchymal Stromal Cells

Transfusion. Aug, 2007  |  Pubmed ID: 17655588

Human multipotent mesenchymal stromal cells (MSCs) are promising candidates for a growing spectrum of regenerative and immunomodulatory cellular therapies. Translation of auspicious experimental results into clinical applications has been limited by the dependence of MSC propagation from fetal bovine serum (FBS).

Roscovitine in B-chronic Lymphocytic Leukemia Cells: High Apoptosis-inducing Efficacy and Synergism with Alemtuzumab Independent of the Patients' Pretreatment Status

Haematologica. Sep, 2007  |  Pubmed ID: 17768132

Roscovitine induced apoptosis in isolated B-chronic lymphocytic leukemia cells of 25 patients of whom nine with relapsed and seven with fludarabine-refractory disease. It was synergistic with alemtuzumab and restored sensitivity to alemtuzumab in initially alemtuzumab-resistant samples. Observed roscovitine-induced up-regulation of CD52 surface expression may be one of the underlying mechanisms for this synergism.

Rapid Large-scale Expansion of Functional Mesenchymal Stem Cells from Unmanipulated Bone Marrow Without Animal Serum

Tissue Engineering. Part C, Methods. Sep, 2008  |  Pubmed ID: 18620484

Adult mesenchymal stem cells (MSCs) are considered as valuable mediators for tissue regeneration and cellular therapy. This study was performed to develop conditions for regularly propagating a clinical quantity of > 2 x 10(8) MSCs without animal serum from small bone marrow (BM) aspiration volumes within short time. We established optimized culture conditions with pooled human platelet lysate (pHPL) replacing fetal bovine serum (FBS) for MSC propagation. MSC quality, identity, purity, and function were assessed accordingly. Biologic safety was determined by bacterial/fungal/mycoplasma/endotoxin testing and genomic stability by array comparative genomic hybridization (CGH). We demonstrate that unmanipulated BM can be used to efficiently initiate MSC cultures without the need for cell separation. Just diluting 1.5-5 mL heparinized BM per 500 mL minimum essential medium supplemented with L-glutamine, heparin, and 10% pHPL sufficiently supported the safe propagation of 7.8 +/- 1.5 x 10(8) MSCs within a single 11- to 16-day primary culture under defined conditions. This procedure also resulted in sustained MSC colony recovery. MSC purity, immune phenotype, and in vitro differentiation potential fully matched current criteria. Despite high proliferation rate, MSCs showed genomic stability in array CGH. This easy single-phase culture procedure can build the basis for standardized manufacturing of MSC-based therapeutics under animal serum-free conditions for dose-escalated cellular therapy and tissue engineering.

Clinical Protocols for the Isolation and Expansion of Mesenchymal Stromal Cells

Transfusion Medicine and Hemotherapy : Offizielles Organ Der Deutschen Gesellschaft Fur Transfusionsmedizin Und Immunhamatologie. 2008  |  Pubmed ID: 21512644

SUMMARY: Multipotent mesenchymal stromal cells (MSCs) are currently exploited in numerous clinical trials to investigate their potential in immune regulation, hematopoiesis, and tissue regeneration. The low frequency of MSCs necessitates cell expansion to achieve transplantable numbers. The challenge is to assure safe and high-quality cell production. GMP(Good Manufacturing Practice)-graded cell processing such as cell preparation, culture, and manipulation is mandatory for the progress of such advanced cell therapy. This review summarizes protocols to isolate MSCs from bone marrow and adipose tissue and to expand MSCs for clinical use focussing on culture media composition as well as culture devices and assays to ensure and control quality of the final product.

Platelet-derived Growth Factors for GMP-compliant Propagation of Mesenchymal Stromal Cells

Bio-medical Materials and Engineering. 2009  |  Pubmed ID: 20042793

Stem cell-based therapies are a promising prospect for regenerative medicine. Particularly, human multipotent mesenchymal stromal cells (MSCs) are currently in focus regarding their regenerative and immune modulating capacities. An increasing number of clinical trials investigating MSC efficiency and safety are ongoing. Ex vivo propagation of human MSCs is considered to be a prerequisite for MSC therapy. The to date standard use of fetal bovine serum in cell culture bears risks including xenoimmunization and transmission of pathogens. Alternatively, human platelet-derived growth factors have been efficiently implemented into routine MSC expansion protocols. In compliance with good manufacturing practice we established an effective time- and resource-saving procedure for MSC propagation in an animal serum-free system. Bone marrow was seeded without manipulation directly in pooled human platelet lysate (pHPL) and L-glutamine supplemented minimum essential medium without antibiotics. Clinical scale expanded MSCs were harvested already after primary culture. MSC quality, identity, purity and function were assessed according to a defined panel of release criteria and comparative genomic hybridization was used to determine genomic stability. Because various potential risks of MSCs have recently been reported, further research is required to prove efficiency and long-term safety of human MSCs for cell therapy.

The Particle Gel Immunoassay As a Rapid Test to Rule out Heparin-induced Thrombocytopenia?

The Journal of Thoracic and Cardiovascular Surgery. Mar, 2009  |  Pubmed ID: 19258119

Humanized Large-scale Expanded Endothelial Colony-forming Cells Function in Vitro and in Vivo

Blood. Jun, 2009  |  Pubmed ID: 19321860

Endothelial progenitor cells are critically involved in essential biologic processes, such as vascular homeostasis, regeneration, and tumor angiogenesis. Endothelial colony-forming cells (ECFCs) are endothelial progenitor cells with robust proliferative potential. Their profound vessel-forming capacity makes them a promising tool for innovative experimental, diagnostic, and therapeutic strategies. Efficient and safe methods for their isolation and expansion are presently lacking. Based on the previously established efficacy of animal serum-free large-scale clinical-grade propagation of mesenchymal stromal cells, we hypothesized that endothelial lineage cells may also be propagated efficiently following a comparable strategy. Here we demonstrate that human ECFCs can be recovered directly from unmanipulated whole blood. A novel large-scale animal protein-free humanized expansion strategy preserves the progenitor hierarchy with sustained proliferation potential of more than 30 population doublings. By applying large-scale propagated ECFCs in various test systems, we observed vascular networks in vitro and perfused vessels in vivo. After large-scale expansion and cryopreservation phenotype, function, proliferation, and genomic stability were maintained. For the first time, proliferative, functional, and storable ECFCs propagated under humanized conditions can be explored in terms of their therapeutic applicability and risk profile.

Human Alternatives to Fetal Bovine Serum for the Expansion of Mesenchymal Stromal Cells from Bone Marrow

Stem Cells (Dayton, Ohio). Sep, 2009  |  Pubmed ID: 19544413

Mesenchymal stromal cells (MSCs) are promising candidates for novel cell therapeutic applications. For clinical scale manufacturing, human factors from serum or platelets have been suggested as alternatives to fetal bovine serum (FBS). We have previously shown that pooled human serum (HS) and thrombin-activated platelet releasate in plasma (tPRP) support the expansion of adipose tissue-derived MSCs. Contradictory results with bone marrow (BM)-derived MSCs have initiated a comprehensive comparison of HS, tPRP, and pooled human platelet lysate (pHPL) and FBS in terms of their impact on MSC isolation, expansion, differentiation, and immunomodulatory activity. In addition to conventional Ficoll density gradient centrifugation, depletion of lineage marker expressing cells (RosetteSep) and CD271+ sorting were used for BM-MSC enrichment. Cells were cultured in medium containing either 10% FBS, HS, tPRP, or pHPL. Colony-forming units and cumulative population doublings were determined, and MSCs were maximally expanded. Although both HS and tPRP comparable to FBS supported isolation and expansion, pHPL significantly accelerated BM-MSC proliferation to yield clinically relevant numbers within the first two passages. MSC quality and functionality including cell surface marker expression, adipogenic and osteogenic differentiation, and immunosuppressive action were similar in MSCs from all culture conditions. Importantly, spontaneous cell transformation was not observed in any of the culture conditions. Telomerase activity was not detected in any of the cultures at any passage. In contrast to previous data from adipose tissue-derived MSCs, pHPL was found to be the most suitable FBS substitute in clinical scale BM-MSC expansion.

A Case of Generalized MALT Lymphoma with IgM Paraproteinemia and Peripheral Blood Involvement

Annals of Hematology. Feb, 2010  |  Pubmed ID: 19582453

Replicative Senescence-associated Gene Expression Changes in Mesenchymal Stromal Cells Are Similar Under Different Culture Conditions

Haematologica. Jun, 2010  |  Pubmed ID: 20053868

Research on mesenchymal stromal cells has created high expectations for a variety of therapeutic applications. Extensive propagation to yield enough mesenchymal stromal cells for therapy may result in replicative senescence and thus hamper long-term functionality in vivo. Highly variable proliferation rates of mesenchymal stromal cells in the course of long-term expansions under varying culture conditions may already indicate different propensity for cellular senescence. We hypothesized that senescence-associated regulated genes differ in mesenchymal stromal cells propagated under different culture conditions.

Prevention of Oxidative Stress in Porcine Islet Isolation

Journal of Artificial Organs : the Official Journal of the Japanese Society for Artificial Organs. Apr, 2010  |  Pubmed ID: 20204442

High yields of pure and viable porcine islet cells (PICs) to be used for microencapsulation are crucial for successful xenotransplantation. Mechanical disruption of the pancreas, enzymes used for digestion, digestion temperature and time are among the factors known to cause oxidative stress and to impact on the yield, purity and viability of PICs. The aim of our study was to optimize conventional procedures in order to minimize the oxidative stress that occurs during the isolation and purification of PICs. Porcine pancreatic tissue was harvested at a local slaughterhouse, and 15 consecutive isolations of PICs were performed with a modified automated Ricordi method (Graz method) using a shorter digestion time, a lower digestion temperature and minimal mechanical stress. PICs were purified with the Lymphoprep density gradient medium. Purity and viability were assessed immediately after the isolation process and after overnight culture. PIC function was tested in glucose stimulation experiments and insulin concentration was determined by ELISA. Oxidative stress was assessed by measuring isoprostanes (IP), malondialdehyde (MDA) and lipase levels using a HPLC-based, colorimetric liquid assay or ELISA, respectively. The mean yield of PICs was 3479 +/- 542 IEQs/g pancreas, with 96.4% viability and 97.7% purity. There was no significant loss in PIC viability after overnight culture. Insulin secretion in response to glucose was not impaired after isolation and purification. IP, MDA and lipase levels did not change significantly during the isolation procedure. With our new Graz method we seem to have succeeded in preventing oxidative stress and achieving high yields of pure and viable PICs.

How to Track Cellular Aging of Mesenchymal Stromal Cells?

Aging. Apr, 2010  |  Pubmed ID: 20453259

Mesenchymal stromal cells (MSC) are currently tested in a large number of clinical trials and raise high hope in regenerative medicine. These cells have to be expanded in vitro before transplantation and several studies demonstrated that long-term culture evokes continuous changes in MSC: proliferation rate decays, the cell size increases, differentiation potential is affected, chromosomal instabilities may arise and molecular changes are acquired. Long-term culture of cell preparations might also have therapeutic consequences, although this has hardly been addressed in ongoing trials so far. Reliable therapeutic regimens necessitate quality control of cellular products. This research perspective summarizes available methods to track cellular aging of MSC. We have demonstrated that gene expression changes and epigenetic modifications are continuously acquired during replicative senescence. Molecular analysis of a suitable panel of genes might provide a robust tool to assess efficiency and safety of long-term expansion.

Pro-angiogenic Induction of Myeloid Cells for Therapeutic Angiogenesis Can Induce Mitogen-activated Protein Kinase P38-dependent Foam Cell Formation

Cytotherapy. Apr, 2011  |  Pubmed ID: 21128706

Clinical trials for therapeutic angiogenesis use blood- or bone marrow-derived hematopoietic cells, endothelial progenitor cells (EPC) and mesenchymal stromal cells (MSC) for vascular regeneration. Recently concerns have emerged that all three cell types could also contribute to atherosclerosis by foam cell formation. Therefore, we asked whether human myelomonocytic cells, EPC or MSC can accumulate lipid droplets (LD) and develop into foam cells.

Immunomodulative Efficacy of Bone Marrow-derived Mesenchymal Stem Cells Cultured in Human Platelet Lysate

Journal of Clinical Immunology. Dec, 2011  |  Pubmed ID: 21887517

Human mesenchymal stem cells (hMSCs) are considered to be a promising tool for novel cell-based therapies. Clinical applications in solid organ transplantation were hampered by the dependence on animal serum for hMSCs clinical scale expansion until substitution with human platelet lysate (HPL) became a promising alternative. Therefore we focused on a direct comparison of immunomodulatory properties of hMSCs cultured in HPL or fetal calf serum (FCS). Phenotypic characterization, detection of cytokine secretion and effects on alloantigen- and mitogen-induced lymphocyte proliferation as well as degranulation of cytomegalovirus-specific cytotoxic T cells were applied in potency assays. We demonstrated that HPL-cultured MSCs have comparable immunomodulatory capacities to their FCS-cultured counterparts. The observed immunomodulatory properties include a beneficial inhibitory effect on immune cell proliferation and an unaffected viral T cell immunity. Thus, culturing hMSCs in HPL generates an efficient and safe expansion combined with intriguing immunomodulatory properties making these cells an attractive cell therapeutic tool.

Endothelial Progenitor Cells: Quod Erat Demonstrandum?

Current Pharmaceutical Design. Oct, 2011  |  Pubmed ID: 21919881

A constantly growing body of research has been performed mainly over the past decade and a half, aiming to facilitate our still limited understanding of the biology and function of various different cell types which collectively have been termed endothelial progenitor cells. This review intends to critically outline aspects of terminology, origin and applicability of the somatic progenitors which are thought to maintain integrity and support regeneration of the inner lining of vessels through proliferation. Despite reasonable progress in the field, we are still not confident regarding the precise phenotype and function of endothelial progenitor cells. Model systems that have been developed to study the vascular regenerative potential of human endothelial progenitor cells in animal models in vivo present principle tools for testing new agents that modulate vascular homeostasis and regeneration.

Globular Domain of Adiponectin: Promising Target Molecule for Detection of Atherosclerotic Lesions

Biologics : Targets & Therapy. 2011  |  Pubmed ID: 22022204

Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions.

Third-party Mesenchymal Stromal Cell Infusion is Associated with a Decrease in Thrombotic Microangiopathy Symptoms Observed Post-hematopoietic Stem Cell Transplantation

Pediatric Transplantation. Dec, 2011  |  Pubmed ID: 22151234

Ansari M, Strunk D, Schallmoser K, Delcò C, Rougemont A-L, Moll S, Villard J, Gumy-Pause F, Chalandon Y, Parvex P, Passweg J, Ozsahin H, Kindler V. Third-party mesenchymal stromal cell infusion is associated with a decrease in thrombotic microangiopathy symptoms observed post-hematopoietic stem cell transplantation. Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S. Abstract:  TA-TMA is a pathology that occurs after allogenic HSC transplantation with an incidence of 4-13%, and represents one of the most severe vascular damage related with this therapy. We report here the case of a nine-yr-old girl suffering from a severe refractory aplastic anemia who received an unrelated, 9/10 HLA-matched HSC. Soon after transplantation, the patient developed a graft-versus-host disease (GvHD), a TA-TMA, and renal insufficiency. These pathologies remained refractory to the various treatments undertaken and required several hospitalizations in the intensive care unit. On day 106 post-HSC transfusion, after several episodes of intensive care, the patient was infused with mismatched, third-party MSCs. Schizocyte levels rapidly decreased after MSC infusion, and two wk later, most biological parameters returned to normal. Erythrocyte and thrombocyte transfusions were discontinued, and the patient remained stable for 10 wk. Thereafter, TA-TMA symptoms, viral reactivation, pleural and cardiac effusions reappeared and lead to the death of the patient. Our observations suggest that allogenic MSC infusion may decrease the symptoms of TA-TMA, but further investigation is required to determine how and when MSC should be infused to develop a long-lasting protective effect.

Human Dermis Harbors Distinct Mesenchymal Stromal Cell Subsets

The Journal of Investigative Dermatology. Mar, 2012  |  Pubmed ID: 22048731

Multipotent mesenchymal stromal cells (MSCs) are found in a variety of adult tissues including human dermis. These MSCs are morphologically similar to bone marrow-derived MSCs, but are of unclear phenotype. To shed light on the characteristics of human dermal MSCs, this study was designed to identify and isolate dermal MSCs by a specific marker expression profile, and subsequently rate their mesenchymal differentiation potential. Immunohistochemical staining showed that MSC markers CD73/CD90/CD105, as well as CD271 and SSEA-4, are expressed on dermal cells in situ. Flow cytometric analysis revealed a phenotype similar to bone marrow-derived MSCs. Human dermal cells isolated by plastic adherence had a lower differentiation capacity as compared with bone marrow-derived MSCs. To distinguish dermal MSCs from differentiated fibroblasts, we immunoselected CD271(+) and SSEA-4(+) cells from adherent dermal cells and investigated their mesenchymal differentiation capacity. This revealed that cells with increased adipogenic, osteogenic, and chondrogenic potential were enriched in the dermal CD271(+) population. The differentiation potential of dermal SSEA-4(+) cells, in contrast, appeared to be limited to adipogenesis. These results indicate that specific cell populations with variable mesenchymal differentiation potential can be isolated from human dermis. Moreover, we identified three different subsets of dermal mesenchymal progenitor cells.