| 1. |
- 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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| 2. |
- Brisby, Helena, 1965, et al.
(författare)
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Moderate Physical Exercise Results in Increased Cell Activity in Articular Cartilage of the Knee Joint in Rats.
- 2013
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Ingår i: Cells, tissues, organs. - : S. Karger AG. - 1422-6421 .- 1422-6405. ; 198:3, s. 237-248
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Tidskriftsartikel (refereegranskat)abstract
- Background: Moderate exercise regimens have shown minor positive effects on matrix turnover in articular cartilage (AC), while effects at cellular level, e.g. proliferation, are scarcely described. Aim: The aim of this study was to investigate the effects of moderate exercise on cell proliferation and recruitment of cells possibly active in regeneration in different regions of cartilage in the rat knee joint. Methods: Eighteen rats were orally given 5-bromo-2-deoxyuridine (BrdU) for 14 days for in vivo DNA labeling. Nine rats underwent treadmill training for 50 min/day, 5 days/week (exercise group), and 9 rats served as controls (no exercise). Animals were sacrificed after 14, 56 and 105 days, and knee joints were harvested. BrdU+ cells were visualized immunohistochemically (IHC) and counted in AC, posterior stem cell niche (PN), potential migration route (PMR; area between PN and the AC border), potential migration area (PMA; region between PN and AC including PN) and epiphyseal cartilage plate (EP) of the tibia and femur. Results: Compared to controls, in the exercise group BrdU+ cells/mm(2) were increased on days 14 (p = 0.022) and 105 (p = 0.045) in AC of the tibia and on day 105 (p = 0.014) in AC of the femur. BrdU+ cell numbers were increased in the PMR region of the tibia on days 14 (p = 0.023) and 105 (p = 0.0018) and in the PMR region of the femur on day 105 (p = 0.0099) as well as in the PMA region of the tibia (p = 0.0008) and femur (p = 0.0080) on day 105. No significant differences in BrdU+ cells/mm(2) were seen in PN or EP between the groups at any time point. Regarding collagen 2A1 expression and proteoglycan accumulation, no significant differences between groups were detected. Conclusions: The results indicate increased cell activity in AC in response to physical exercise and may help to understand the complexity of AC regeneration in the normal mammal knee joint. © 2013 S. Karger AG, Basel.
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| 3. |
- 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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| 4. |
- Nicolaos, Papadimitriou, 1972, et al.
(författare)
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Intradiscal Injection of Iron-Labeled Autologous Mesenchymal Stromal Cells in Patients With Chronic Low Back Pain: A Feasibility Study With 2 Years Follow-Up
- 2021
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Ingår i: International Journal of Spine Surgery. - : International Journal of Spine Surgery. - 2211-4599. ; 15:6, s. 1201-1209
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Degeneration of the intervertebral disc is considered to be central in pain pathogenesis in patients suffering from chronic low back pain (LBP). In recent years, the injection of mesenchymal stromal cells (MSCs) into the disc to arrest or reverse the degenerative process has been proposed as an alternative therapy. The aim of the present study was to investigate the feasibility of using iron-labeled MSCs for intradiscal injection in patients with long-standing LBP. Methods: Ten patients (7 men, 3 women, mean age 40 years, range 26-53) with chronic LBP and confirmed disc degeneration on magnetic resonance imaging (MRI) were recruited from the waiting list for planned surgery. Injection of autologous, expanded, and iron-labeled bone marrow-derived MSCs (BM-MSCs) into 1 or 2 disc levels was undertaken. Follow-up consisted of monitoring of adverse events, regular MRI examinations, and collection of patient-reported outcome measures (PROMs) for a minimum of 2 years. Results: No complications could be detected, neither clinically nor on MRI. No statistically significant improvement was seen for PROMs on a group level up to 2 years postinjection. Three of 10 patients opted to proceed with the initially planned surgery within the first year and 2 more within 3 years postinjection. Conclusion: Results from this pilot cohort study show that injection of autologous expanded iron-labeled BM-MSCs is a safe procedure, in accordance with the existing body of evidence. The clinical result warrants further larger studies. © 2021 ISASS.
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