Sex chiniaerism and germ cell distribution in a series of chimaeric mice

Development ◽  
1975 ◽  
Vol 33 (1) ◽  
pp. 205-216
Author(s):  
Anne McLaren
Keyword(s):  
Bone Marrow ◽  
Blood Cells ◽  
Chromosome Analysis ◽  
Chromosome Morphology ◽  
Mixed Population ◽  
Cell Distribution ◽  
Single Sex ◽  
Xx Males

1. Of 30 mice born from aggregation of embryos from a multiple recessive strain with F1 embryos carrying the contrasting alleles, 4 females and 20 males proved to be overtly chimaeric. 2. Three XX/XX females, five XY/XY males and eight XY/XX males were identified by chromosome analysis. Thus 50 % of the population analysed were sex chimaeras, and all of these developed as phenotypic males, though one showed evidence of hermaphroditism. 3. In seven XY/XX chimaeras that bred, the genetic component undergoing spermatogenesis coincided in every case with the component identified by chromosome morphology as XY. 4. The F1 component predominated in metaphase plates derived from cultured blood cells. Comparison with direct preparations from bone marrow suggested selection in favour of F1 cells, either through differential proliferation of stem cells in vivo or differential response to phytohaemagglutinin in vitro. 5. In XY/XX males, the percentage of XX cells detected varied from 1 % to 98 % in blood, and from 0 % to 80 % in bone marrow. 6. Of eight ‘single-sex’ chimaeras progeny-tested (three XX/XX, five XY/XY), only one showed evidence of a mixed population of germ cells. The proportion of the two types of progeny varied significantly from litter to litter, but was unrelated to the age of the male.

Single-Stranded Oligonucleotide Binding to P-Selectin Inhibits Adhesion of Sickle Red Blood Cells and Leukocytes to Endothelial Cells in Sickle Cell Model Mice: Novel Therapeutics for Vaso-Occlusive Episodes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1545-1545
Author(s):  
Diana Gutsaeva ◽  
James Parkerson ◽  
Robert G Schaub ◽  
Jeffrey Kurz ◽  
Alvin Head
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Carotid Artery ◽  
Blood Cells ◽  
Research Funding ◽  
Leukocyte Rolling ◽  
Adhesive Interactions

Abstract Abstract 1545 Poster Board I-568 To date, a variety of therapeutic approaches to sickle cell disease (SCD) have been explored, however, knowledge about the efficacy of anti-adhesive agents in this disorder is limited. In SCD, P-selectin expressed on endothelial cells plays a key role in leukocyte recruitment as well as in the adhesion of sickle red blood cells (sRBC) to the endothelium. The interaction of P-selectin and its ligands is thus likely to contribute to impairment of the microvascular flow and thereby to the development of painful vaso-occlusive episodes. Studies with anti-P-selectin antibody and P-selectin-deficient mice support the notion that P-selectin-directed interventions may be a potential approach to the treatment of vaso-occlusive episodes in SCD. Aptamers, short single-stranded oligonucleotides, have been developed for a wide range of therapeutic targets (Keefe & Schaub, 2008). Aptamers bind molecular targets with high affinity and specificity, do not elicit immune responses, and can be readily delivered to the vascular compartment intravenously or subcutaneously. Although anti-P-selectin aptamers have been shown to inhibit leukocyte rolling in vitro and to display efficacy in mouse models for inflammation, the anti-adhesion activity of anti-P-selectin aptamers has never been evaluated in SCD. The purpose of this study was to determine in vivo whether the anti-P-selectin aptamer ARC5690 can inhibit adhesion of sickle RBC and leukocytes to vascular endothelial cells in the bone marrow microvasculature of SCD model mice. Knockout-transgenic SCD mice generated by Ryan et al. (Ryan et al., 1997) were used in this study. SCD mice were injected with 20 mg/kg ARC5690, scrambled aptamer ARC5694 (negative control), or vehicle (saline). Anti-P-selectin monoclonal antibody was also used as a positive control. After 2.5 hours, the mice were subjected to 1 hour of hypoxia (12% O2 in air) followed by 1 hour of reoxygenation at room air. Intravital observations of the bone marrow microcirculation were performed to monitor adhesive interactions between blood cells and endothelial cells. Leukocytes were labeled in vivo with rat anti mouse CD45 antibody conjugated with PE which were infused via the carotid artery. Sickle RBC were obtained from donor mice, fluorescently labeled in vitro with 2,7-bis-(carboxyethyl)-5-(and-6) carboxyfluorescein, and infused through the carotid artery. Effects of ARC5690 on sRBC and leukocyte adhesive interactions were compared to those of ARC5694 and vehicle. Administration of the anti-P-selectin aptamer ARC5690 significantly reduced sRBC adhesion (p<0.05) in SCD mice compared to those treated with vehicle. The anti-adhesive activity of ARC5690 for sRBC was comparable to anti-P-selectin monoclonal antibody, whereas the scrambled aptamer did not show any anti-adhesive activity. We also studied the effects of the anti-P-selectin-specific ARC5690 on leukocyte flow dynamics. Mice pretreated with ARC5690, but not those treated with scrambled aptamer ARC5694, showed a greater than four-fold decrease in leukocyte rolling (p<0.001) and a six-fold decrease in adhesion (p<0.001) compared with vehicle-treated mice. Again, the anti-adhesive activity of ARC5690 and its effect on leukocyte rolling and adhesion were similar to those of the anti-P-selectin antibody. Furthermore, ARC5690 improved blood circulation compared to vehicle-treated mice as shown by increased RBC velocity and d wall shear rates. In conclusion, our study demonstrates significant anti-adhesive activities of ARC5690, which reduces the adhesion of sRBC and leukocytes to the vascular endothelium in SCD model mice. ARC5690 may represent a novel therapeutic strategy that can be used to treat vaso-occlusive episodes in SCD Disclosures Gutsaeva: Archemix Corporation: Research Funding. Parkerson:Archemix Corporation: Research Funding. Schaub:Archemix: Research Funding. Kurz:Archemix Corporation: Employment. Head:Archemix Corporation: Research Funding.

scholarly journals Preclinical Mechanistic Studies Investigating Neutrophil and Lymphoid Cell Depletion By IMGN529, a CD37-Targeting Antibody-Drug Conjugate (ADC)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3119-3119 ◽  
Author(s):  
Jutta Deckert ◽  
Jose F. Ponte ◽  
Jennifer A. Coccia ◽  
Leanne Lanieri ◽  
Sharon Chicklas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Peripheral Blood Cells ◽  
Employment Equity ◽  
Normal Human ◽  
Equity Ownership

Abstract CD37 is a surface antigen widely expressed on malignant B cells in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). In normal tissues, CD37 expression is restricted to lymphoid tissues and blood cells, with high levels of expression on B lymphocytes and low levels on non-B lymphoid and myeloid cells. IMGN529 is a CD37-targeting ADC currently in a Phase I clinical study in adult patients with relapsed or refractory NHL (NCT01534715). This ADC uniquely combines the intrinsic pro-apoptotic and immune effector activities of its anti-CD37 antibody component with the potent cytotoxic mechanism provided by targeted delivery of its maytansinoid payload, DM1. In the Phase I study, IMGN529 has demonstrated early evidence of clinical activity. A reduction in lymphocyte counts was also observed in the majority of patients after dosing, consistent with the proposed mechanism of action of a CD37-targeted therapy. However, in the initial dose-escalation phase, some patients experienced transient, early-onset neutropenia. To investigate the potential mechanisms of this transient neutropenia observed in patients, different pre-clinical models were considered and utilized to recapitulate clinical findings. In vitro studies with peripheral blood cells from normal human donors demonstrated that incubation with IMGN529 for 1 hour or 24 hours resulted in significant B-cell depletion with no apparent neutrophil depletion detected, similar to observations after rituximab treatment. In contrast, alemtuzumab treatment in vitro resulted in both B-cell and neutrophil depletion. This is consistent with the high level of CD37 expression on target B cells and the relatively low CD37 expression level on other blood cells. Analysis of cytokine release by normal human donor peripheral blood cells incubated with IMGN529 revealed increased levels of IL-8, CCL2 (MCP-1) and CCL4 (MIP-1β), but not IL-6 or TNF, to a similar extent as rituximab but less pronounced than alemtuzumab. An anti-murine CD37 antibody was identified to enable in vivo studies in a murine model and characterize CD37 expression on murine blood cells. Similar to the expression profile of CD37 in human peripheral blood cells, CD37 expression on murine peripheral blood cells was highest in B cells, with much lower expression seen on T cells and granulocytes. In vivo activity of the anti-muCD37 antibody and the corresponding ADC, with the same SMCC-DM1 linker-payload combination as IMGN529, was evaluated to discern antibody and payload-mediated events in comparison to the classic cytotoxic cyclophosphamide (CPA). Treatment of C57/B6 mice with 1-10 mg/kg of anti-muCD37 antibody or anti-muCD37 ADC resulted in a significant decrease in absolute lymphocyte counts (ALC) lasting greater than 7 days and a transient decrease in absolute neutrophil counts (ANC) lasting 1-2 days. A non-targeted control SMCC-DM1 ADC had no effect on ALC or ANC counts, suggesting the decrease is a CD37-mediated effect. In contrast, treatment with CPA resulted in an ALC decrease with similar kinetics but a more pronounced ANC decline. No impact on bone marrow lymphocyte, myeloid or erythroid precursor cell counts was observed in response to the anti-muCD37 antibody or anti-muCD37 ADC, whereas CPA treatment caused reduced cellularity with a decrease in the percentage of mature myeloid precursors and neutrophils in bone marrow. Elevated levels of CCL2 and CCL4 chemokines were detected in mouse plasma after anti-muCD37 ADC treatment, which may contribute to a redistribution of circulating neutrophils into peripheral tissues. Studies are currently underway to assess neutrophil distribution in murine tissues post anti-muCD37 ADC treatment. Current preclinical studies provide no clear evidence for direct IMGN529-mediated depletion of normal human neutrophils in the context of B-cell depletion in vitro. In vivo studies with an anti-muCD37 ADC recapitulate transient peripheral lymphopenia and neutropenia with no impact on bone marrow precursors observed, indicative of a different mechanism than classic chemotherapy-induced bone marrow myelosuppression. These preliminary results suggest a role for chemokine-mediated neutrophil redistribution following CD37 engagement, which is the subject of further studies. Disclosures Deckert: ImmunoGen, Inc.: Employment, Equity Ownership. Ponte:ImmunoGen, Inc.: Employment, Equity Ownership. Coccia:ImmunoGen, Inc.: Employment, Equity Ownership. Lanieri:ImmunoGen, Inc.: Employment, Equity Ownership. Chicklas:ImmunoGen, Inc.: Employment, Equity Ownership. Yi:ImmunoGen, Inc.: Employment, Equity Ownership. Watkins:ImmunoGen, Inc.: Employment, Equity Ownership. Ruiz-Soto:ImmunoGen, Inc.: Employment, Equity Ownership; sanofi: Employment. Romanelli:ImmunoGen, Inc.: Employment, Equity Ownership; sanofi: Employment. Lutz:ImmunoGen, Inc.: Employment, Equity Ownership.

Mechanism of Action of PLX-R18, a Placental-Derived Cellular Therapy for the Treatment of Radiation-Induced Bone Marrow Failure

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2417-2417 ◽  
Author(s):  
Racheli Ofir ◽  
Lena Pinzur ◽  
Akyüz Levent ◽  
Zami Aberman ◽  
Raphael Gorodetsky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mechanism Of Action ◽  
Blood Cells ◽  
Treated Group ◽  
Cell Counts ◽  
Animal Survival ◽  
Radiation Induced ◽  
Human Cytokines

Abstract Bone marrow (BM) failure occurs in individuals who fail to produce sufficient red blood cells, white blood cells, or platelets. This may be a result of damage to hematopoietic stem cells by a congenital defect or by exposure to a noxious substance or factor. PLX-R18 are 3D-expanded placenta-derived cells, with biological properties including a profound capacity to protect and regenerate bone marrow. The cells secrete a broad array of cytokines including G-CSF, IL-6, MCP-1, MCP-3 and GRO that contribute to the reconstitution of the hematopoietic and immune systems. To assess their therapeutic potential, PLX-RAD cells were administered to C3H/HeN male mice intramuscularly, one and five days following 7.7 Gy total body irradiation. Body weight and animal survival were monitored for 3 weeks, then the animals were euthanized for BM and blood analysis. In the PLX-R18-treated group, 10 out of 11 (91%) animals survived, compared to only 4 out of 9 in the vehicle treated group (44%), (P < 0.05). Weight reduction after irradiation was also improved in the PLX-RAD treated mice where the average weight loss was less than 10% compared to almost 20% for vehicle-treated controls. Consistent with the improved survival, cell counts of all the three hematopoietic lineages were significantly increased in the BM and blood of PLX-R18 treated mice as compared to the control animals, and attained close to normal levels. Analysis of plasma in the irradiated treated animals detected the presence of critical, PLX-R18-derived (human) cytokines as well as alterations in the equivalent murine cytokines, suggesting a direct role of PLX-R18 secreted cytokines in animal survival. Interestingly, human cytokines were detected only after irradiation and were not present in the plasma of sham non-irradiated animals treated with PLX-R18. This may imply that the active in vivo cytokine secretion by PLX-R18 is a response to signals from the environment in the irradiated animals. Already by day 4-6 after irradiation, the number of colony forming progenitors in the BM of PLX-R18 treated animals was significantly higher than in control animals suggesting that earlier regeneration of BM induced by PLX-R18 secreted cytokines results in improved blood counts and increased survival. Studies in vitro demonstrated that PLX-R18-derived conditioned medium induced the formation of all colony types in a methyl cellulose colony formation assay as well as a 3.1 fold-increase in the number of migrating cells in a BM migration assay compared to the SDF-1-supplemented positive control. These results, in vivo and in vitro, reveal key clues to the resolution of the underlying mechanism of action. Administration of the novel cell product PLX-R18 markedly improved survival and recovery of the three hematopoietic blood lineages after radiation induced BM failure indicating potential as a highly effective therapy for general radiation-induced BM damage, or in a nuclear disaster scenario. Further clinical studies are planned. Disclosures Ofir: Pluristem ltd: Employment. Pinzur:Pluristem ltd: Employment. Aberman:Pluristem ltd: Employment. Gorodetsky:Pluristem ltd: Consultancy. Volk:Pluristem ltd: Consultancy.

Apoptosis in circulating PMN: increased susceptibility in L-selectin-deficient PMN

1997 ◽  
Vol 272 (6) ◽  
pp. H2852-H2858 ◽  
Author(s):  
K. T. Matsuba ◽  
S. F. Van Eeden ◽  
S. G. Bicknell ◽  
B. A. Walker ◽  
S. Hayashi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Fragmentation ◽  
Peripheral Blood ◽  
Magnetic Beads ◽  
Mixed Population ◽  
Enzyme Linked Immunosorbent Assay ◽  
Morphological Criteria ◽  
Increased Susceptibility

Previous work from our laboratory has shown that polymorphonuclear leukocytes (PMN) lose L-selectin as they age in the circulation. The present study was designed to examine the relationship between PMN age and susceptibility to apoptosis in the circulation using L-selectin as a marker of PMN age in rabbits. L-selectin-deficient leukocytes were separated from a mixed population of PMN in leukocyte-rich plasma using magnetic beads. Apoptosis was measured both with both morphological criteria and by determining the level of DNA fragmentation. The L-selectin-deficient cells separated in vitro showed morphological features of apoptosis (P < 0.01) and had higher levels of DNA fragmentation (P < 0.01) than the mixed population of PMN from which they were obtained. To determine if aging had a similar effect in vivo, PMN were labeled in the bone marrow with 5'-bromo-2'-deoxyuridine (BrdU) and L-selectin levels (immunocytochemistry) and DNA fragmentation (sandwich enzyme-linked immunosorbent assay) were measured in BrdU-labeled PMN in peripheral blood. The results showed that the peak release of BrdU-labeled PMN from the bone marrow into peripheral blood was associated with high levels of L-selectin expression, and these PMN had the lowest levels of DNA fragmentation. These results confirm that the level of L-selectin expression can be used as a marker of cell age and extend this observation by showing that aging in the circulation is associated with an increased susceptibility to apoptosis.

scholarly journals Origin, Kinetics, and characteristics of pulmonary macrophages in the normal steady state.

1979 ◽  
Vol 149 (6) ◽  
pp. 1504-1518 ◽  
Author(s):  
A B van oud Alblas ◽  
R van Furth
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Mixed Population ◽  
Cell Renewal ◽  
Pulmonary Tissue ◽  
Macrophage Population ◽  
Pulmonary Macrophage ◽  
Pulmonary Macrophages

Pulmonary macrophages of mice in the steady state were isolated by lavage with PBS containing EDTA and subsequent enzymatic digestion of tissue with pronase and DNA-ase. By this method, the total pulmonary macrophage population was obtained in two cell suspensions, one with a pure population of pulmonary alveolar macrophages (PAM) and the other with a mixed population of pulmonary alveolar and pulmonary tissue macrophages (PTM). The morphological, cytochemical, and functional characteristics of both PAM and PTM were like those of mature tissue macrophages except for the presence of C3 receptors. These receptors were almost absent on PAM and present on a larger number of cells in the mixed population of PAM and PTM. The total pulmonary macrophage population of mice in the steady state is approximately equal to 2 x 10(6), of which about 93% are PAM and about 7% are PTM. In labeling experiments with 3H-thymidine, the low in vitro labeling indices (less than 3%) for both PAM and the mixture of PAM and PTM, showed that both are essentially nondividing cells. In vivo labeling studies showed an increase in the number of labeled macrophages that can only be attributed to labeled monocytes migrating into the lungs. Additional evidence was provided by a decrease in the labeling indices of pulmonary macrophages when mice were treated with hydrocortisone acetate, which causes a severe monocytopenia, thus preventing monocyte influx into the lungs. Confirmation of the bone marrow origin was obtained in mice labeled after x-irradiation with partial bone marrow shielding: labeled pulmonary macrophages were found in the exposed lungs. In all experiments, the labeling indices were identical in the two macrophage populations isolated. These results show that the influx of monocytes is the source of cell renewal for the pulmonary macrophages. No indications for an interstitial division or maturation compartment in the lung were found. Quantitation of the efflux of labeled monocytes from the blood, and the number of labeled pulmonary macrophages, showed that in the steady state about 15% of the monocytes leaving the circulation become pulmonary macrophages and that the turnover time of pulmonary macrophages is approximately equal to 27 d.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

Bone Marrow Niches for Skeletal Progenitor Cells and their Inhabitants in Health and Disease

2019 ◽  
Vol 14 (4) ◽  
pp. 305-319 ◽  
Author(s):  
Marietta Herrmann ◽  
Franz Jakob
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Cell Populations ◽  
Surface Markers ◽  
Bone Marrow Niches

The bone marrow hosts skeletal progenitor cells which have most widely been referred to as Mesenchymal Stem or Stromal Cells (MSCs), a heterogeneous population of adult stem cells possessing the potential for self-renewal and multilineage differentiation. A consensus agreement on minimal criteria has been suggested to define MSCs in vitro, including adhesion to plastic, expression of typical surface markers and the ability to differentiate towards the adipogenic, osteogenic and chondrogenic lineages but they are critically discussed since the differentiation capability of cells could not always be confirmed by stringent assays in vivo. However, these in vitro characteristics have led to the notion that progenitor cell populations, similar to MSCs in bone marrow, reside in various tissues. MSCs are in the focus of numerous (pre)clinical studies on tissue regeneration and repair.Recent advances in terms of genetic animal models enabled a couple of studies targeting skeletal progenitor cells in vivo. Accordingly, different skeletal progenitor cell populations could be identified by the expression of surface markers including nestin and leptin receptor. While there are still issues with the identity of, and the overlap between different cell populations, these studies suggested that specific microenvironments, referred to as niches, host and maintain skeletal progenitor cells in the bone marrow. Dynamic mutual interactions through biological and physical cues between niche constituting cells and niche inhabitants control dormancy, symmetric and asymmetric cell division and lineage commitment. Niche constituting cells, inhabitant cells and their extracellular matrix are subject to influences of aging and disease e.g. via cellular modulators. Protective niches can be hijacked and abused by metastasizing tumor cells, and may even be adapted via mutual education. Here, we summarize the current knowledge on bone marrow skeletal progenitor cell niches in physiology and pathophysiology. We discuss the plasticity and dynamics of bone marrow niches as well as future perspectives of targeting niches for therapeutic strategies.

scholarly journals Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 268
Author(s):  
Jonathan Ribot ◽  
Cyprien Denoeud ◽  
Guilhem Frescaline ◽  
Rebecca Landon ◽  
Hervé Petite ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Adipogenic Differentiation ◽  
Therapeutic Modality ◽  
Multipotent Stromal Cells ◽  
Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

scholarly journals Multimodal Diagnostics of Microrheologic Alterations in Blood of Coronary Heart Disease and Diabetic Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 76
Author(s):  
Anastasia Maslianitsyna ◽  
Petr Ermolinskiy ◽  
Andrei Lugovtsov ◽  
Alexandra Pigurenko ◽  
Maria Sasonko ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Optical Methods ◽  
Diabetic Patients ◽  
Aggregation Index ◽  
Significant Difference

Coronary heart disease (CHD) has serious implications for human health and needs to be diagnosed as early as possible. In this article in vivo and in vitro optical methods are used to study blood properties related to the aggregation of red blood cells in patients with CHD and comorbidities such as type 2 diabetes mellitus (T2DM). The results show not only a significant difference of the aggregation in patients compared to healthy people, but also a correspondence between in vivo and in vitro parameters. Red blood cells aggregate in CHD patients faster and more numerously; in particular the aggregation index increases by 20 ± 7%. The presence of T2DM also significantly elevates aggregation in CHD patients. This work demonstrates multimodal diagnostics and monitoring of patients with socially significant pathologies.

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