The Traceability of Mesenchymal Stromal Cells After Injection Into Degenerated Discs in Patients with Low Back Pain

Henriksson, Helena Barreto; Papadimitriou, Nikolaos; Hingert, Daphne; Baranto, Adad; Lindahl, Anders; Brisby, Helena

doi:10.1089/scd.2019.0074

Cited by 34 publications

(29 citation statements)

References 47 publications

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“…Only one study of intralesional injection of MSCs and their biodistribution was observed. Henriksson et al [118] injected MSCs into intervertebral discs in 4 patients. Discs were explanted at 8 and 28 months post injection.…”

Section: Distribution Of Mscs After Intralesional Injection In Humansmentioning

confidence: 99%

Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

Sánchez‐Díaz

Quiñones-Vico

Torre

et al. 2021

JCM

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Mesenchymal Stromal Cells (MSCs) are of great interest in cellular therapy. Different routes of administration of MSCs have been described both in pre-clinical and clinical reports. Knowledge about the fate of the administered cells is critical for developing MSC-based therapies. The aim of this review is to describe how MSCs are distributed after injection, using different administration routes in animal models and humans. A literature search was performed in order to consider how MSCs distribute after intravenous, intraarterial, intramuscular, intraarticular and intralesional injection into both animal models and humans. Studies addressing the biodistribution of MSCs in “in vivo” animal models and humans were included. After the search, 109 articles were included in the review. Intravenous administration of MSCs is widely used; it leads to an initial accumulation of cells in the lungs with later redistribution to the liver, spleen and kidneys. Intraarterial infusion bypasses the lungs, so MSCs distribute widely throughout the rest of the body. Intramuscular, intraarticular and intradermal administration lack systemic biodistribution. Injection into various specific organs is also described. Biodistribution of MSCs in animal models and humans appears to be similar and depends on the route of administration. More studies with standardized protocols of MSC administration could be useful in order to make results homogeneous and more comparable.

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Section: Distribution Of Mscs After Intralesional Injection In Humansmentioning

confidence: 99%

Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

Sánchez‐Díaz

Quiñones-Vico

Torre

et al. 2021

JCM

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“…Determination of the duration of detectability of IS-labeled ASCs was not one of the objectives of this study; however, a previous study using Lapine's intervertebral disc xenotransplantation model showed ASCs could be detected by histologic examination for at least 3 months and that the mean viability of IS-labeled MSCs was 99% at 1 month after transplantation which is not significantly different from non-iron sucrose-labeled MSCs (95%) [ 28 ]. In a human study, IS-labeled MSCs could be detected for at least 6–12 months in a transplanted intervertebral disc; extracellular iron particles were found in only one patient who had received a transplant 2.5 years previously; however, clinical outcomes, side effects and adverse reactions to IS-labeled ASCs and MSCs transplantation in human subjects were not reported in that study [ 26 ]. Currently, many aspects of IS-labeled ASCs and MSCs, e.g., the duration of cell detection by MRI, the longevity of cells after transfection in a human subject, the proliferation potential and clinical results of IS-labelled ASCs/MSCs transplantation, are largely unknown as there has not been much research on those topics.…”

Section: Discussionmentioning

confidence: 99%

“…One mg/ml (complete medium) of iron sucrose (Venofer®) was added to the basal culture medium then the mixture was re-incubated at 37 °C for 16 h [ 17 ]. The dose was based on that used in previous studies [ 22 , 26 ] After that, the transfected medium was washed out 3 times using PBS and then trypsinized and was then split for: Cell viability evaluation using the Trypan-blue exclusion method [ 27 ] using a hemocytometer and a light microscope. Immunophenotypes assessment to confirm MSCs characteristics with flow cytometry using positive cell surface markers (CD73 and CD90) and negative cell surface markers (CD 34 and CD45) (eBioscience, USA).…”

Section: Methodsmentioning

confidence: 99%

Using iron sucrose-labeled adipose-derived mesenchymal stem cells in 1.5 and 3 T MRI tracking: An in vitro study

Tangchitphisut

Srikaew

Phongkitkarun

et al. 2020

Heliyon

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Objectives The objective of this study was to investigate iron sucrose labeling in mesenchymal stem cell (MSCs) tracking. Background Adipose-derived mesenchymal stem cell-based therapy is a promising strategy for promoting musculoskeletal repair. Methods Iron sucrose-labeled adipose-derived mesenchymal stem cells (IS-labeled ASCs) were tracked using T2-and T2∗-weighted sequences by 1.5 and 3 T MRI in an in vitro model. ASCs were isolated from cosmetic liposuction specimens. ASCs from passages 4–6 were labeled with iron sucrose (Venofer®) which was added to the cell culture medium. Pre- and post-iron sucrose labeled ASCs were evaluated for cell surface immunophenotypes. Cell viability as well as chondrogenic, adipogenic and osteogenic differentiation of IS-labeled-ASCs were evaluated. The IS-labeled ASCs were titrated into microtubes at 1 × 10 3 , 1 × 10 4 , 1 × 10 5 and 1 × 10 6 cells/ml/microtube and their intensities were determined by 1.5 and 3T MRI using T2-and T2∗-weighted sequences. Results The expression markers of IS-labeled ASCs from flow cytometry were equivalent to control. The mean cell viability was 97.73 ± 2.06%. Cell differentiations of IS-labeled ASCs were confirmed in each lineage using specific staining solutions. T2∗-weighted sequences (T2∗) were able to detect iron sucrose labeled-ASCs at a minimum of 1 × 10 5 cells/ml/microtube using 1.5 and 3T MRI, but the detection sensitivity was lower with T2-weighted sequences (T2). Conclusions Iron sucrose incubation is a safe alternative method for ASCs labeling and tracking using MRI following treatment. Clinicians and researchers should be able to visualize the location of ASCs engraftment without secondary surgical investigation involving tissue sampling.

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“…Indeed, several in vitro and in vivo reports have showed that stem cells become rapidly undetectable soon after or a few weeks following transplantation as a consequence of nutrient deprivation and low pH as well as due to the pressure generated during the procedure itself. 37,38,40 In a recent study from Henriksson et al, 41 iron sucrose-labelled autologous BM-MSCs were injected in the IVDs of 4 patients subsequently undergoing discectomy and fusion surgery. The results showed that viable MSCs and their progeny were retrieved in harvested IVD tissues up to 8 months postinjection as both large cell clusters and solitary cells.…”

Section: The Effect Of Stem Cells In the Degenerative Ivd Environment Differentiation Into Ivd-like Cellsmentioning

confidence: 99%

Stem Cells and Intervertebral Disc Regeneration Overview—What They Can and Can't Do

et al. 2021

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Background: Low back pain (LPB) is the main cause of disability worldwide with enormous socioeconomic burdens. A major cause of LBP is intervertebral disc degeneration (IDD): a chronic, progressive process associated with exhaustion of the resident cell population, tissue inflammation, degradation of the extracellular matrix and dehydration of the nucleus pulposus. Eventually, IDD may lead to serious sequelae including chronic LBP, disc herniation, segmental instability, and spinal stenosis, which may require invasive surgical interventions. However, no treatment is actually able to directly tackle IDD and hamper the degenerative process. In the last decade, the intradiscal injection of stem cells is raising as a promising approach to regenerate the intervertebral disc. This review aims to describe the rationale behind a regenerative stem cell therapy for IDD as well as the effect of stem cells following their implantation in the disc environment according to preclinical studies. Furthermore, actual clinical evidence and ongoing trials will be discussed, taking into account the future perspective and current limitations of this cutting-edge therapy.Methods: A literature analysis was performed for this narrative review. A database search of PubMed, Scopus and ClinicalTrials.gov was conducted using ''stem cells'' combined with ''intervertebral disc'', ''degeneration'' and ''regeneration'' without exclusion based on publication date. Articles were firstly screened on a title-abstract basis and, subsequently, full-text were reviewed. Both preclinical and clinical studies have been included.Results: The database search yielded recent publications from which the narrative review was completed.Conclusions: Based on available evidence, intradiscal stem cell therapy has provided encouraging results in terms of regenerative effects and reduction of LBP. However, multicenter, prospective randomized trials are needed in order confirm the safety, efficacy and applicability of such a promising treatment.

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The Traceability of Mesenchymal Stromal Cells After Injection Into Degenerated Discs in Patients with Low Back Pain

Cited by 34 publications

References 47 publications

Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

Using iron sucrose-labeled adipose-derived mesenchymal stem cells in 1.5 and 3 T MRI tracking: An in vitro study

Stem Cells and Intervertebral Disc Regeneration Overview—What They Can and Can't Do

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