Clinically relevant preservation conditions for mesenchymal stem/stromal cells derived from perinatal and adult tissue sources
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ABSTRACT:
SUBMITTER: Ngo A
PROVIDER: S-EPMC8581317 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo develop a system to guide interpretation of scores generated from the newly developed item response theory (IRT)-based Functional Assessment in Acute Care Multidimensional Computerized Adaptive Test (FAMCAT), which assesses 3 important domains of function: Mobility, Daily Activities, and Applied Cognition.DesignCross-sectional data was used to inform a modified Delphi approach to establish FAMCAT cutpoints delineating various functional ability levels.SettingLarge midwestern academic teaching hospital.ParticipantsPatients hospitalized to an inpatient medical service (N=2049).InterventionsNot applicable.Main outcome measuresFAMCAT Basic Mobility, Daily Activity, and Applied Cognition scores.ResultsIRT-based score estimation data was successfully integrated with expert clinical feedback using a modified Delphi process to arrive at consensus yielding 4 functional level strata (ranging from bed-based mobility to independent mobility) for both the FAMCAT Mobility and Daily Activity scales; 1 cutpoint was supported to delineate 2 functional strata for Applied Cognition.ConclusionsMeaningful cutpoints were established for each FAMCAT domain using a data-informed, modified Delphi process for achieving consensus. The resulting FAMCAT interpretation guide may be used to develop an ability-matched mobility preservation program and identify patients who may require a higher level of supervision based on the resulting FAMCAT scores.
| S-EPMC8767567 | biostudies-literature
Project description:Human perinatal tissue is an abundant source of mesenchymal stromal cells(MSCs) and lacks the ethical concerns. Perinatal MSCs can be obtained from various tissues as like amnion, chorion, and umbilical cord. Still, little is known of the distinct nature of each MSC type. In this study, we successfully isolated and cultured MSCs from amnion(AMSCs), chorion(CMSCs), and umbilical cord(UC-MSCs). Proliferation potential was different among them, that AMSCs revealed the lowest proliferation rate due to increased Annexin V and senescence-associated β-galactosidase positive cells. We demonstrated distinct characteristic gene expression according to the source of the original tissue using microarray. In particular, genes associated with apoptosis and senescence including CDKN2A were up-regulated in AMSCs. In CMSCs, genes associated with heart morphogenesis and blood circulation including HTR2B were up-regulated. Genes associated with neurological system processes including NPY were up-regulated in UC-MSCs. Quantitative RT-PCR confirmed the gene expression data. And in vitro differentiation of MSCs demonstrated that CMSCs and UC-MSCs had a more pronounced ability to differentiate into cardiomyocyte and neural cells, respectively. This study firstly demonstrated the innate tissue-specific differentiation potency of perinatal MSCs which can be helpful in choosing more adequate cell sources for better outcome in a specific disease.
| S-EPMC4820697 | biostudies-literature
Project description:BackgroundThe multimodal properties of mesenchymal stromal cells (MSCs), particularly their ability to modulate immune responses is of high interest in translational research. Pro-inflammatory, hypoxic, and 3D culture priming are promising and often used strategies to improve the immunosuppressive potency of MSCs, but the underlying mechanisms are not well understood. Therefore, the aims of this study were (i) to compare the effects of pro-inflammatory, hypoxic, and 3D culture priming on the in vitro immunosuppressive potential of MSCs, (ii) to assess if immunosuppressive priming effects are temporally preserved under standard and translationally relevant culture conditions, and (iii) to investigate if the three priming strategies engage the same immunosuppressive mechanisms.MethodsFunctional in vitro T cell suppressive potency measurements were conducted to assess the impact of pro-inflammatory, hypoxic, and 3D culture priming on the immunosuppressive potential of human bone marrow-derived MSCs. Primed MSCs were either cultured under standard cell culture conditions or translationally relevant culture conditions, and their transcriptomic adaptations were monitored over time. Next-generation sequencing was performed to assess if different priming strategies activate distinct immunosuppressive mechanisms.Results(i) Pro-inflammatory, hypoxic, and 3D culture priming induced profound transcriptomic changes in MSCs resulting in a significantly enhanced T cell suppressive potential of pro-inflammatory and 3D culture primed MSCs. (ii) Priming effects rapidly faded under standard cell culture conditions but were partially preserved under translationally relevant conditions. Interestingly, continuous 3D culture priming of MSCs maintained the immunosuppressive potency of MSCs. (iii) Next-generation sequencing revealed that priming strategy-specific differentially expressed genes are involved in the T cell suppressive capacity of MSCs, indicating that different priming strategies engage distinct immunosuppressive mechanisms.ConclusionPriming can be a useful approach to improve the immunosuppressive potency of MSCs. However, future studies involving primed MSCs should carefully consider the significant impact of translationally relevant conditions on the preservation of priming effects. Continuous 3D culture could act as a functionalized formulation, supporting the administration of MSC spheroids for a sustainably improved immunosuppressive potency.
| S-EPMC10916130 | biostudies-literature
Project description:Introduction:Stem cells for therapy are often suspended in a preservation solution, such as normal saline or lactated Ringer's solution, for a short time before intravenous infusion. However, these solutions are not necessarily ideal for maintaining cell viability and preventing the sedimentation of cells during storage and infusion. In this study, we attempted to optimize the compositions of preservation solutions, which could affect the efficacy and safety of stem cell therapy. Methods:We determined the characteristics of a preservation solution that would optimize cell viability and the percentage of cells in the supernatant using human adipose-derived mesenchymal stromal cells (hADSCs). We compared solutions that differed by electrolytes (e.g., normal saline and Ringer's solution) and the concentrations of dextran 40 and trehalose. The effects of the solutions on hADSCs were evaluated by assessing cell surface markers, colony-forming capacity, differentiation potential, and cell concentrations in the infusion line. Results:Optimized preservation solutions consisted of lactated Ringer's solution with 3% trehalose without or with 5% dextran 40 (LR-3T and LR-3T-5D, respectively). The cell viabilities after 24 h of storage at 5 °C in LR-3T and LR-3T-5D were 94.9% ± 2.4% and 97.6% ± 2.4%, respectively. The percentage of cells in the supernatant after 1 h of storage at room temperature in LR-3T-5D was 83.5% ± 7.6%. These solutions preserved the percentage of cell surface marker-positive cells, the colony-forming capacity, and the adipogenic and osteogenic differentiation ability in hADSCs for at least 24 h after preservation at 5 °C and 25 °C. Discussion:We determined the optimal composition of preservation solutions for hADSCs and confirmed the effects of these solutions on cell viability and the stability of cell characteristics in vitro. Our results suggest that LR-3T and LR-3T-5D can help maintain the quality of stem cells for therapy during preservation and infusion. However, further in vivo research is needed on the efficacy and safety of the solutions in different therapeutic cell lines before clinical use.
| S-EPMC6970134 | biostudies-literature
Project description:Physical exercise (PE) has unquestionable beneficial effects on health, which likely extend into several organ-to-cell physiological processes. At the cell scale, endogenous mesenchymal stromal cells (MSCs) contribute to tissue repair, although their repair capacities may be insufficient in paucicellular or severely damaged tissues. For this reason, MSC transplantation holds great promise for tissue repair. With the goals of understanding if PE has beneficial effects on MSC biology and if PE potentiates their role in tissue repair, we reviewed literature reports regarding the effects of PE on MSC properties (specifically, proliferation, differentiation, and homing) and of a combination of PE and MSC transplantation on tissue repair (specifically neural, cartilage, and muscular tissues). Contradictory results have been reported; interpretation is complicated because various and different species, cell sources, and experimental protocols, specifically exercise programs, have been used. On the basis of these data, the effects of exercise on MSC proliferation and differentiation depend on exercise characteristics (type, intensity, duration, etc.) and on the characteristics of the tissue from which the MSCs were collected. For the in vitro studies, the level of strain (and other details of the mechanical stimulus), the time elapsed between the end of exposure to strain and MSC collection, the age of the donors, as well as the passage number at which the MSCs are evaluated also play a role. The combination of PE and MSC engraftment improves neural, cartilage, and muscular tissue recovery, but it is not clear whether the effects of MSCs and exercise are additive or synergistic.
| S-EPMC6850997 | biostudies-literature
Project description:BACKGROUND:Mesenchymal stromal cells (MSC) are a heterogeneous population of multipotent progenitors used in the clinic because of their immunomodulatory properties and their ability to differentiate into multiple mesodermal lineages. Although bone marrow (BM) remains the most common MSC source, cord blood (CB) can be collected noninvasively and without major ethical concerns. Comparative studies comprehensively characterizing the MSC phenotype across several tissue sources are still lacking. This study provides a 246-antigen immunophenotypic analysis of BM- and CB-derived MSC aimed at identifying common and strongly expressed MSC markers as well as the existence of discriminating markers between the two sources. METHODS:BM-MSC (n = 4) were expanded and analyzed as bulk (n = 6) or single clones isolated from the bulk culture (n = 3). CB-MSC (n = 6) were isolated and expanded as single clones in 5/6 samples. The BM-MSC and CB-MSC phenotype was investigated by flow cytometry using a panel of 246 monoclonal antibodies. To define the markers common to both sources, those showing the smallest variation between samples (coefficient of variation of log2 fold increase ≤ 0.5, n = 59) were selected for unsupervised hierarchical cluster analysis (HCL). Differentially expressed markers were identified by directly comparing the expression of all 246 antigens between BM-MSC and CB-MSC. RESULTS:Based on HCL, 18 markers clustered as strongly expressed in BM-MSC and CB-MSC, including alpha-smooth muscle antigen (SMA), beta-2-microglobulin, CD105, CD13, CD140b, CD147, CD151, CD276, CD29, CD44, CD47, CD59, CD73, CD81, CD90, CD98, HLA-ABC, and vimentin. All except CD140b and alpha-SMA were suitable for the specific identification of ex-vivo expanded MSC. Notably, only angiotensin-converting enzyme (CD143) was exclusively expressed on BM-MSC. CD143 expression was tested on 10 additional BM-MSC and CB-MSC and on 10 umbilical cord- and adipose tissue-derived MSC samples, confirming that its expression is restricted to adult sources. CONCLUSIONS:This is the first study that has comprehensively compared the phenotype of BM-MSC and CB-MSC. We have identified markers that could complement the minimal panel proposed for the in-vitro MSC definition, being shared and strongly expressed by BM- and CB-derived MSC. We have also identified CD143 as a marker exclusively expressed on MSC derived from adult tissue sources. Further studies will elucidate the biological role of CD143 and its potential association with tissue-specific MSC features.
| S-EPMC5771027 | biostudies-literature
Project description:Cardiovascular events are the primary cause of death among dialysis patients. While arteriovenous fistulas (AVFs) are the access of choice for hemodialysis patients, AVF creation can lead to a volume overload (VO) state in the heart. We developed a three-dimensional (3D) cardiac tissue chip (CTC) with tunable pressure and stretch to model the acute hemodynamic changes associated with AVF creation to complement our murine AVF model of VO. In this study, we aimed to replicate the hemodynamics of murine AVF models in vitro and hypothesized that if 3D cardiac tissue constructs were subjected to "volume overload" conditions, they would display fibrosis and key gene expression changes seen in AVF mice. Mice underwent either an AVF or sham procedure and were sacrificed at 28 days. Cardiac tissue constructs composed of h9c2 rat cardiac myoblasts and normal adult human dermal fibroblasts in hydrogel were seeded into devices and exposed to 100 mg/10 mmHg pressure (0.4 s/0.6 s) at 1 Hz for 96 h. Controls were exposed to "normal" stretch and experimental group exposed to "volume overload". RT-PCR and histology were performed on the tissue constructs and mice left ventricles (LVs), and transcriptomics of mice LVs were also performed. Our tissue constructs and mice LV both demonstrated cardiac fibrosis as compared to control tissue constructs and sham-operated mice, respectively. Gene expression studies in our tissue constructs and mice LV demonstrated increased expression of genes associated with extracellular matrix production, oxidative stress, inflammation, and fibrosis in the VO conditions vs. control conditions. Our transcriptomics studies demonstrated activated upstream regulators related to fibrosis, inflammation, and oxidative stress such as collagen type 1 complex, TGFB1, CCR2, and VEGFA and inactivated regulators related to mitochondrial biogenesis in LV from mice AVF. In summary, our CTC model yields similar fibrosis-related histology and gene expression profiles as our murine AVF model. Thus, the CTC could potentially play a critical role in understanding cardiac pathobiology of VO states similar to what is present after AVF creation and may prove useful in evaluating therapies.
| S-EPMC9978753 | biostudies-literature
Project description:Many immune-mediated conditions are associated with a dysregulated imbalance toward a Th1 response leading to disease onset, severity, and damage. Many of the therapies such as immunomodulators or anti-TNF-? antibodies often fall short in preventing disease progression and ameliorating disease conditions. Thus, new therapies that can target inflammatory environments would have a major impact in preventing the progression of inflammatory diseases. We investigated the role of human stromal cells derived from the amniotic fluid (AFSCs), the placenta (PLSCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in modulating the inflammatory response of in vitro-stimulated circulating blood-derived immune cells. Immune cells were isolated from the blood of healthy individuals and stimulated in vitro with antigens to activate inflammatory responses to stimuli. AFSC, BM-MSCs, and PLSCs were cocultured with stimulated leukocytes, neutrophils, or lymphocytes. Inflammatory cytokine production, neutrophil migration, enzymatic degranulation, T cell proliferation, and subsets were evaluated. Coculture of all three stromal cell types decreased the gene expression of inflammatory cytokines and enzymes such as IL-1?, IFN-?, TNF-?, neutrophil elastase, and the transcription factor NF-?B in lipopolysaccharide-stimulated leukocytes. With isolated phytohemagglutinin-stimulated peripheral blood mononuclear cells, cells coculture leads to a decrease in lymphocyte proliferation. This effect correlated with decreased numbers of Th1 lymphocytes and decreased secreted levels of IFN-?.
| S-EPMC6954711 | biostudies-literature
Project description:Human limbus-derived stromal/mesenchymal stem cells (hLMSC) can be one of the alternatives for the treatment of corneal scars. However, reliable methods of storing and transporting hLMSC remains a serious translational bottleneck. This study aimed to address these limitations by encapsulating hLMSC in alginate beads. Encapsulated hLMSC were kept in transit in a temperature-conditioned container at room temperature (RT) or stored at 4?°C for 3-5 days, which is the likely duration for transporting cells from bench-to-bedside. Non-encapsulated cells were used as controls. Post-storage, hLMSC were released from encapsulation, and viability-assessed cells were plated. After 48 and 96-hours in culture the survival, gene-expression and phenotypic characteristics of hLMSC were assessed. During transit, the container maintained an average temperature of 18.6?±?1.8?°C, while the average ambient temperature was 31.4?±?1.2?°C (p?=?0.001). Encapsulated hLMSC under transit at RT were recovered with a higher viability (82.5?±?0.9% and 76.9?±?1.9%) after 3 (p?=?0.0008) and 5-day storage (p?=?0.0104) respectively as compared to 4?°C (65.2?±?1.2% and 64.5?±?0.8% respectively). Cells at RT also showed a trend towards greater survival-rates when cultured (74.3?±?2.9% and 67.7?±?9.8%) than cells stored at 4?°C (54.8?±?9.04% and 52.4?±?8.1%) after 3 and 5-days storage (p?>?0.2). Non-encapsulated cells had negligible viability at RT and 4?°C. Encapsulated hLMSC (RT and 4?°C) maintained their characteristic phenotype (ABCG2, Pax6, CD90, p63-?, CD45, CD73, CD105, Vimentin and Collagen III). The findings of this study suggest that alginate encapsulation is an effective method of hLMSC preservation offering high cell viability over prolonged durations in transit at RT, therefore, potentially expanding the scope of cell-based therapy for corneal blindness.
| S-EPMC6861256 | biostudies-literature
Project description:Perinatal complications in both term- and preterm-born infants are a leading cause of neonatal morbidities and mortality. Infants face different challenges in the neonatal intensive care unit with long-term morbidities such as perinatal brain injury and bronchopulmonary dysplasia being particularly devastating. While advances in perinatal medicine have improved our understanding of the pathogenesis, effective therapies to prevent and/or reduce the severity of these disorders are still lacking. The potential of mesenchymal stem/stromal cell (MSC) therapy has emerged during the last two decades, and an increasing effort is conducted to address brain- and lung-related morbidities in neonates at risk. Various studies support the notion that MSCs have protective effects. MSCs are an easy source and may be readily available after birth in a clinical setting. MSCs' mechanisms of action are diverse, including migration and homing, release of growth factors and immunomodulation, and the potential to replace injured cells. Here, we review the pathophysiology of perinatally acquired brain and lung injuries and focus on MSCs as potential candidates for therapeutic strategies summarizing preclinical and clinical evidence.
| S-EPMC4751100 | biostudies-literature