| 1. |
- Aked, Joseph, et al.
(författare)
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Attitudes to Stem Cell Therapy among Ischemic Stroke Survivors in the Lund Stroke Recovery Study
- 2017
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 26:8, s. 566-572
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies suggest that stem cell therapy (SCT) may improve poststroke recovery, and clinical trials investigating safety are ongoing. However, knowledge about patients' attitudes to SCT in stroke is limited. We evaluated the knowledge and attitudes to this therapeutic approach as well as possible factors influencing this among stroke patients potentially suitable for SCT. Consecutive first-ever acute ischemic stroke patients aged 20-75 years with NIH stroke scale scores 1-18 were included. Exclusion criteria were severe comorbidities or infratentorial stroke. Clinical follow-up after 3-5 years assessed severity of residual stroke symptoms, cognitive function, functional status, patient-reported outcome, and comorbidity, and after receiving standardized information, the participants also completed an eight-item questionnaire on knowledge and attitudes about SCT. The relationships between clinical variables and positive attitude to SCT were assessed with logistic regression analyses. Of 108 patients included at baseline, 84 participated at follow-up and completed the questionnaire. In total, 12% had prior knowledge of SCT. When informed, 63% were positive toward it and 36% reported willingness to participate in SCT trials. Only 5%-8% expressed ethical considerations regarding different stem cell sources. Positive attitudes to SCT were associated with male gender (OR: 3.74; 95% CI: 1.45-9.61; P < 0.01) and better patient-reported outcome (OR: 1.02; 95% CI: 1.00-1.04; P < 0.05). In conclusion, stroke patients had limited prior knowledge of SCT, yet attitudes were positive among the majority after receiving standardized and neutral information. Gender and degree of stroke recovery may influence attitudes to SCT, indicating a need for targeted information to improve knowledge about SCT.
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| 4. |
- Barreto Henriksson, Helena, et al.
(författare)
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The Traceability of Mesenchymal Stromal Cells After Injection Into Degenerated Discs in Patients with Low Back Pain.
- 2019
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Ingår i: Stem cells and development. - : Mary Ann Liebert Inc. - 1557-8534 .- 1547-3287. ; 28:17, s. 1203-1211
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain is a major health issue and one main cause to this condition is believed to be intervertebral disc (IVD) degeneration. Stem cell therapy for degenerated discs using mesenchymal stromal cells (MSCs) has been suggested. The aim of the study was to investigate the presence and distribution pattern of autologous MSCs transplanted into degenerated IVDs in patients and explanted posttransplantation. IVD tissues from four patients (41, 45, 47, and 47 years of age) participating in a clinical feasibility study on MSC transplantation to degenerative discs were investigated. Three patients decided to undergo fusion surgery at time points 8 months and one patient at 28 months posttransplantation. Pretransplantation, MSCs from bone marrow aspirate were isolated by centrifugation in FICOLL® test tubes and cultured (passage 1). Before transplantation, MSCs were labeled with 1mg/mL iron sucrose (Venofer®) and 1×106 MSCs were transplanted into degenerated IVDs. At the time point of surgery, IVD tissues were collected. IVD tissue samples were fixated, embedded in paraffin, and sections prepared. IVD samples were stained with Prussian Blue, by which iron deposits are visualized and examined (light microscopy). Immunohistochemistry (IHC), including SOX9 (sex determining region Y box 9), Coll2A1 (collagen 2A1), and cell viability (TUNEL) were performed. Cells positive for iron deposits were observed in IVD tissues (3/4 patients). The cells/iron deposits were observed in clusters and/or as solitary cells in regions in IVD tissue samples [regions of interest (ROIs)]. By IHC, SOX9- and Coll2A1-positive cells were detected in the same regions as the detected cells/iron deposits. A few nonviable cells were detected by TUNEL assay in ROIs. Results demonstrated that MSCs, labeled with iron sucrose, transplanted into degenerated IVDs were detectable 8 months posttransplantation. The detected cellular activity indicates that MSCs have differentiated into chondrocyte-like cells and that the injected MSCs and/or their progeny have survived since the cells were found in large cluster and as solitary cells which were distributed at different parts of the IVD.
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| 5. |
- Brisby, Helena, 1965, et al.
(författare)
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The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: A descriptive study in humans
- 2013
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 22:5, s. 804-814
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain is common and degenerated discs are believed to be a major cause. In non-degenerated intervertebral discs(IVDs) presence of stem-/progenitor cells was recently reported in different mammals (rabbit,rat,pig). Understanding processes of disc degeneration and regenerative mechanisms within degenerated discs(DDs) is important. The aim of the study was to examine presence of local stem-/progenitor cells in human DDs and if these cell-populations could respond to paracrin stimulation in vitro. Tissue biopsies from the IVD region (L3-S1) was collected from 15 patients, age 34-69 years, undergoing surgery (spinal fusion) and mesenchymal stem cells (MSCs)(iliac crest) from two donors. Non-degenerated disc cells were collected from one donor(scoliosis) and chordoma tissue was obtained from(positive control, stem cell markers) two donors. The IVD biopsies were investigated for gene- and protein expression of: OCT3/4, CD105, CD90, STRO-1 and NOTCH1. DD cell cultures(pellet mass) were performed with conditioned media from MSCs and non-degenerated IVD cells. Pellets were investigated after 7, 14, 28 days for the same stem cell markers as above. Gene expression of OCT3/4 and STRO-1 was detected in 13/15 patient samples, CD105 in 14/15 samples and CD90 and NOTCH1 was detected 15/15 samples. Immunohistochemistry analysis supported findings on protein level, in cells sparsely distributed in DDs tissues. DDs cell-cultures displayed more undifferentiated appearance with increased expression of CD105, CD90, STRO-1, OCT3/4, NOTCH1 and JAGGED1 which was observed when cultured in conditioned cell-culture media from MSC compared to cell-cultures cultured with conditioned media from non-degenerated disc cells. Expression of OCT3/4(multipotency marker) and NOTCH1(regulator of cell fate), MSC- markers CD105, CD90 and STRO-1 indicate that primitive cell populations are present within DDs. Furthermore, the possibility to influence cells from DDs by by paracrin signalling /soluble factors from MSCs and from non-degenerated IVD cells was observed in vitro indicating that repair processes within human degenerated discs may be stimulated.
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| 6. |
- Caplan, A, et al.
(författare)
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Author Accountability in Biomedical Research
- 2018
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Ingår i: Stem cells and development. - : Mary Ann Liebert Inc. - 1557-8534 .- 1547-3287. ; 27:24, s. 1671-1673
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Concepcion Cruz-Santos, Maria, et al.
(författare)
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The Role of microRNAs in Animal Cell Reprogramming
- 2016
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 25:14, s. 1035-1049
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Forskningsöversikt (refereegranskat)abstract
- Our concept of cell reprogramming and cell plasticity has evolved since John Gurdon transferred the nucleus of a completely differentiated cell into an enucleated Xenopus laevis egg, thereby generating embryos that developed into tadpoles. More recently, induced expression of transcription factors, oct4, sox2, klf4, and c-myc has evidenced the plasticity of the genome to change the expression program and cell phenotype by driving differentiated cells to the pluripotent state. Beyond these milestone achievements, research in artificial cell reprogramming has been focused on other molecules that are different than transcription factors. Among the candidate molecules, microRNAs (miRNAs) stand out due to their potential to control the levels of proteins that are involved in cellular processes such as self-renewal, proliferation, and differentiation. Here, we review the role of miRNAs in the maintenance and differentiation of mesenchymal stem cells, epimorphic regeneration, and somatic cell reprogramming to induced pluripotent stem cells.
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| 8. |
- Dahlin, Joakim S., et al.
(författare)
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Distinguishing Mast Cell Progenitors from Mature Mast Cells in Mice
- 2015
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 24:14, s. 1703-1711
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells originate from the bone marrow and develop into c-kit(+) FcRI(+) cells. Both mast cell progenitors (MCp) and mature mast cells express these cell surface markers, and ways validated to distinguish between the two maturation forms with flow cytometry have been lacking. Here, we show that primary peritoneal MCp from naive mice expressed high levels of integrin 7 and had a low side scatter (SSC) light profile; whereas mature mast cells expressed lower levels of integrin 7 and had a high SSC light profile. The maturation statuses of the cells were confirmed using three main strategies: (1) MCp, but not mature mast cells, were shown to be depleted by sublethal whole-body -irradiation. (2) The MCp were small and immature in terms of granule formation, whereas the mature mast cells were larger and had fully developed metachromatic granules. (3) The MCp had fewer transcripts of mast cell-specific proteases and the enzyme responsible for sulfation of heparin than mature mast cells. Moreover, isolated peritoneal MCp gave rise to mast cells when cultured in vitro. To summarize, we have defined MCp and mature mast cells in naive mice by flow cytometry. Using this strategy, mast cell maturation can be studied in vivo.
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| 17. |
- Ghazanfari, Roshanak, et al.
(författare)
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Human Non-Hematopoietic CD271pos/CD140alow/neg Bone Marrow Stroma Cells Fulfill Stringent Stem Cell Criteria in Serial Transplantations
- 2016
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 25:21, s. 1652-1658
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Tidskriftsartikel (refereegranskat)abstract
- Human bone marrow contains a population of non-hematopoietic stromal stem/progenitor cells (BMSCs), which play a central role for bone marrow stroma and the hematopoietic microenvironment. However, the precise characteristics and potential stem cell properties of defined BMSC populations have not yet been thoroughly investigated. Using standard adherent colony-forming unit fibroblast (CFU-F) assays, we have previously shown that BMSCs were highly enriched in the nonhematopoietic CD271pos/CD140alow/neg fraction of normal adult human bone marrow. In this study, we demonstrate that prospectively isolated CD271pos/CD140alow/neg BMSCs expressed high levels of hematopoiesis supporting genes and signature mesenchymal and multipotency genes on a single cell basis. Furthermore, CD271pos/CD140alow/neg BMSCs gave rise to non-adherent sphere colonies (mesenspheres) with typical surface marker profile and trilineage in vitro differentiation potential. Importantly, serial transplantations of CD271pos/CD140alow/neg BMSC-derived mesenspheres (single cell and bulk) into immunodeficient NOD scid gamma (NSG) mice showed increased mesensphere numbers and full differentiation potential after both primary and secondary transplantations. In contrast, BMSC self-renewal potential decreased under standard adherent culture conditions. These data therefore indicate that CD271pos/CD140alow/neg BMSCs represent a population of primary stem cells with MSC phenotype and sphere-forming capacity that fulfill stringent functional stem cell criteria in vivo in a serial transplantation setting.
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| 18. |
- Hertegård, Stellan, et al.
(författare)
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Hyaluronan Hydrogels for the Local Delivery of Mesenchymal Stromal Cells to the Injured Vocal Fold
- 2019
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Ingår i: Stem Cells and Development. - : MARY ANN LIEBERT, INC. - 1547-3287 .- 1557-8534. ; 28:17, s. 1177-1190
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stromal cells (MSCs) promote wound healing by expediting the inflammatory phase. Local injection of MSCs into injured vocal folds (VFs) is effective in animal models, suggesting suitability for clinical translation. Despite their therapeutic potential, MSCs do not persist within the VF. This study evaluates whether hyaluronan (HA) hydrogels offer a safe delivery vehicle for local injection of MSCs into VFs, and increase longevity of the cells within the injured tissue. MSCs +/- HA hydrogel were exposed to interleukin (IL)1 beta, IL8, and chemokine (C-C motif) ligand 4, and evaluated for mRNA expression of matrix remodeling genes and secretion of immunomodulatory/prohealing factors. Chemotaxis/invasion in response to inflammation was evaluated. A lapin model of VF injury evaluated in vivo effects of MSCs +/- HA hydrogel on enhancing VF healing. Histological evaluation of inflammation, type I collagen expression, HA hydrogel resorption, and MSC persistence was evaluated at 3 and 25 days after injury. MSCs within HA hydrogel were responsive to their extracellular environment, upregulating immunomodulatory factors when exposed to inflammation. Despite delayed migration out of the gel in vitro, the MSCs did not persist longer within the injured tissue in vivo. MSCs +/- HA hydrogel exerted equivalent dampening of inflammation in vivo. The gel was resorbed within 25 days and no edema was evident. HA hydrogels can be safely used in the delivery of MSCs to injured VFs, minimizing leakage of administered cells. MSCs within the HA hydrogel did not persist longer than those in suspension, but did exert comparable therapeutic effects.
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| 19. |
- Hoeber, Jan, 1986-, et al.
(författare)
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A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord
- 2017
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 26:14, s. 1065-1077
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Tidskriftsartikel (refereegranskat)abstract
- Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (MesoMIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along "bridges" formed by migrating stem cells. Coimplantation of MesoMIM prevented stem cell migration, "bridges" were not formed, and sensory axons failed to enter the spinal cord. MesoMIM applied alone supported sensory axons ingrowth, but without affecting glial scar formation. In vitro, the presence of MesoMIM significantly impaired migration of hscNSPC without affecting their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular "bridges" in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient alternative way to induce sensory axon regeneration, and (3) a combinatorial approach of individually beneficial components is not necessarily additive, but can be counterproductive for axonal growth.
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| 22. |
- Hoogduijn, Martin J, et al.
(författare)
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Effects of freeze-thawing and intravenous infusion on mesenchymal stromal cell gene expression.
- 2016
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1557-8534 .- 1547-3287.
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stromal cells (MSC) are increasingly used as an investigative therapeutic product for immune disorders and degenerative disease. Typically, MSC are isolated from human tissue, expanded in culture and cryopreserved until usage. The safety and efficacy of MSC therapy will depend on the phenotypical and functional characteristics of MSC. The freeze-thawing procedure may change these characteristics. Furthermore, the cells encounter a microenvironment after administration that may impact their properties. It has been demonstrated that the majority of MSC localize to the lungs after intravenous infusion, making this the site to study the effects of the in vivo milieu on administered MSC. In the present study we investigated the effect of freeze-thawing and the mouse lung microenvironment on human adipose tissue-derived MSC. There were effects of freeze-thawing on the whole genome expression profile of MSC, although the effects did not exceed inter-donor differences. There were no major changes in the expression of hemostatic regulators on transcriptional level, but significantly increased expression of procoagulant tissue factor on the surface of thawed adipose MSC, correlating with increased procoagulant activity of thawed cells. Exposure for 2h to the lung microenvironment had a major effect on MSC gene expression and affected several immunological pathways. This indicates that MSC undergo functional changes shortly after infusion and this may influence the efficacy of MSC to modulate inflammatory responses. The results of this study demonstrate that MSC rapidly alter in response to the local milieu and that disease specific conditions may shape MSC after administration.
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| 23. |
- Hu, ZQ, et al.
(författare)
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Cell replacement therapy in the inner ear
- 2006
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Ingår i: Stem cells and development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 15:3, s. 449-459
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Tidskriftsartikel (refereegranskat)
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| 24. |
- Islam, Quamrul, 1952-, et al.
(författare)
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Epigenetic reprogramming of nonreplicating somatic cells for long-term proliferation by temporary cell-cell contact
- 2007
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 16:2, s. 253-268
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Tidskriftsartikel (refereegranskat)abstract
- Embryonic stem (ES) cells are potential sources of tissue regeneration, however, transplanted ES cells produce tumors in the host tissues. In addition, transplantation between genetically unrelated individuals often results in graft rejection. Although the development of patient specific stem cell lines by somatic cell nuclear transfer (SCNT) represents a means of overcoming the problem of rejection, its human application has ethical dilemmas. Adult stem (AS) cells can also differentiate into specialized cells and may provide an alternative source of cells for human applications. In common with other somatic cells, AS cells have limited capacity for proliferation and cannot be produced in large quantities without genetic manipulation. We demonstrate here that nonreplicating mammalian cells can be reprogrammed for long-term proliferation by temporary cell-cell contact through co-culture of AS cells with the GM05267-derived F7 mouse cell line. Subsequent elimination of F7 cells from the co-culture allows proliferation of previously nonreplicating cells, colonies of which can be isolated to produce cell lines. We also demonstrate that the epigenetically reprogrammed AS cells, without the physical transfer of either nuclear or cytoplasmic material from other cells, are capable of long-term proliferation and able to relay signals to other nonreplicating cells to reinitiate proliferation with no addition of recombinant factors. The reported cell amplification procedure is methodologically simple and can be easily reproduced. This procedure allows the production of an unlimited number of cells from a limited number of AS cells, making them an ideal source of cells for applications involving autologous cell transplantation. © Mary Ann Liebert, Inc.
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| 25. |
- Islam, Quamrul, 1952-, et al.
(författare)
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Polyethylene glycol-mediated fusion between primary mouse mesenchymal stem cells and mouse fibroblasts generates hybrid cells with increased proliferation and altered differentiation
- 2006
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 15:6, s. 905-919
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Tidskriftsartikel (refereegranskat)abstract
- Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into different cell lineages with the appropriate stimulation in vitro. Transplantation of MSCs in human and other animal models was found to repair tissues through the fusion of transplanted MSCs with indigenous cells. We have generated mouse-mouse hybrid cell lines in vitro by polyethylene glycol-mediated fusion of primary mouse MSCs with mouse fibroblasts to investigate the characteristics of hybrid cells, including their potentials for proliferation and differentiation. Similar to the parental MSCs, hybrid cells are positive for the cell-surface markers CD29, CD44, CD49e, and Sca-1, aed negative for Gr1, CD11b, CD13, CD18, CD31, CD43, CD45, CD49d, CD90.2, CD445M/B220, and CD117 markers. The hybrid cells also produce a high level of tissue nonspecific alkaline phosphatase compared to the parental cells. Conditioned medium of hybrid cells contain biologically active factors that are capable of stimulating proliferation of other cells. Although the parental MSCs can differentiate into adipogenic and osteogenic lineages, hybrid cells held disparate differentiation capacity. Hybrid cell lines in general have increased proliferative capacity than the primary MSCs. Our study demonstrates that proliferative hybrid cell lines can be generated in vitro by induced fusion of both im-mortal and primary somatic cells with primary MSCs. © Mary Ann Liebert, Inc.
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