Persistence of fluorescent nanoparticle‐labeled bone marrow mesenchymal stem cells
            <i>in vitro</i>
            and after intra‐articular injection

Grady, Sicilia T; Britton, Lorraine; Hinrichs, Katrin; Nixon, Alan J.; Watts, Ashlee E.

doi:10.1002/term.2781

Cited by 10 publications

(15 citation statements)

References 31 publications

(37 reference statements)

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“…In a previous study, we reported no adverse effects of CdSe/ZnS QD labeling on the differentiation potential of adult stem cells isolated from rat pancreas [9]. Similar observations for other stem cell types such as embryonic stem cells, induced pluripotent stem cells or mesenchymal ones have recently been published [10][11][12]. Intriguingly, others have noted changes in the differentiation profile of stem cells after labeling with nanoparticles such as the inhibition of osteogenesis with QD labeled bone marrow mesenchymal stem cells [13][14][15].…”

Section: Introductionsupporting

confidence: 78%

“…The major challenge for cell tracking in vitro and in vivo is long-term and non-invasive monitoring of cell migration and differentiation, as well as surveillance of the regenerative potential [1,22,26]. Exceptional and long-lasting fluorescence properties of quantum dot nanocrystals prone them as an excellent tool for labeling cells with the aim of tracking these cells after transplantation [12,27,28]. Prior to an in vivo application, we gained mandatory knowledge of the effects of QDs on the biocompatibility, proliferation and differentiation capabilities of human epithelial stem cells in vitro in this study.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Human Skin-Derived Stem Cell Characteristics After Non-Invasive Quantum Dot Labeling

Benzin

Schumann

Richter

et al. 2021

Cell Physiol Biochem

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BACKGROUND/AIMS: The use of skin-derived stem cells and stem cells of other origins in regenerative medicine requires knowledge of stem cell fate after transplantation. In order to achieve non-invasive long-term imaging and tracking of transplanted stem cells in preclinical studies, a non-toxic, efficient labeling technique that does not alter stem cell characteristics must be used. Our aim was to investigate a method for such a long-term cell-compatible cell tracer using nanoparticles. METHODS: Nanotechnology, in particular the use of quantum dots (QDs), offers great advantages for this crucial requirement. In this study, we used nanocrystals coated with a specific target peptide that enables delivery into the cytoplasm of cells, resulting in an intense and stable fluorescent labeling. We analyzed the influence of biocompatible CdSe/ZnS-QDs on epidermal stem cells (EpiSCs) isolated from adult human skin. Thereby we analyzed on QD loading, cell proliferation including QD transfer to descendent daughter cells as well as the influence on the differentiation potential of stem cells after QD labeling. RESULTS: FACS analysis revealed a dose-dependent QD incorporation into the cells. Thereby, a high initial concentration of nanocrystals resulted in a more stable long-term labeling. QD labeled cells showed normal viability and unchanged ability to proliferate. The spread of QDs during cell division was monitored by time lapse microscopy and two modes of QD distribution could be observed. Daughter cells either received an equal amount of QDs after cell division, which led to a homogenously faded fluorescence signal, or there was an uneven transmission of QDs, which led to unchanged labeling of one cell and a complete loss of the fluorescence signal of the other cell. The spontaneous differentiation potential remained unaffected after QD exposure, since skin-derived EpiSCs showed an unchanged protein and gene expression profile. CONCLUSION: In summary, we can conclude that QDs offer a successful, non-invasive and efficient labeling technique for EpiSCs, which makes their in vitro and in vivo use in skin regeneration and wound healing models traceable. Nevertheless, the uneven transmission of QDs should not be disregarded and the extent and frequency should be investigated in further studies.

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Section: Introductionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Evaluation of Human Skin-Derived Stem Cell Characteristics After Non-Invasive Quantum Dot Labeling

Benzin

Schumann

Richter

et al. 2021

Cell Physiol Biochem

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“…As the persistence of injected MSCs in the joint is limited[14,22,23], their therapeutic effect is likely to be temporary. A single intra-articular injection of MSCs can therefore no longer be considered as an ‘OA treatment for life’ and repeated intra-articular dosing may have more beneficial effects.…”

Section: Introductionmentioning

confidence: 99%

Comparison of efficacy and safety of single versus repeated intra-articular injection of allogeneic neonatal mesenchymal stem cells for treatment of osteoarthritis of the metacarpophalangeal/metatarsophalangeal joint in horses: A clinical pilot study

et al. 2019

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The purpose of this prospective study was to evaluate the effects of single and repeated intra-articular administration of allogeneic, umbilical cord-derived, neonatal mesenchymal stem cells (MSC) in horses with lameness due to osteoarthritis (OA) of a metacarpophalangeal joint (MPJ). Twenty-eight horses were included. Horses were divided into two groups. Horses in group MSC1 received an MSC injection at M0 and a placebo injection at M1 (1 month after M0). Horses in group MSC2 received MSC injections at M0 and at M1. Joint injections were performed with a blinded syringe. Clinical assessment was performed by the treating veterinarian at M1, M2 and M6 (2 and 6 months after M0), including lameness evaluation, palpation and flexion of the joint. Radiographic examination of the treated joints was performed at inclusion and repeated at M6. Radiographs were anonymized and assessed by 2 ECVDI LA associate members. Short term safety assessment was performed by owner survey. A 2-month rehabilitation program was recommended to veterinarians. There was a significant improvement of the total clinical score for horses in both groups. There was no significant difference in the total clinical score between groups MSC1 and MSC2 at any time point in the study. There was no significant difference in the total radiographic OA score, osteophyte score, joint space width score and subchondral bone score between inclusion and M6. Owner-detected adverse effects to MSC injection were recorded in 18% of the horses. Lameness caused by OA improved significantly over the 6-month duration of the study after treatment with allogeneic neonatal umbilical cord-derived MSCs combined with 8 weeks rest and rehabilitation. There is no apparent clinical benefit of repeated intra-articular administration of MSCs at a 1-month interval in horses with MPJ OA when compared to the effect of a single injection.

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“…A noninvasive means of imaging and tracking the cell fate after in vivo implantation could be extremely valuable. Quantum dots such as fluorescencelabeled mesoporous silica nanoparticles and superparamagnetic iron oxide (SPIO) nanoparticles have been developed for in vitro and in vivo bioimaging [257,258]. The basic principle for the cell-labeling agents is that enough number of nanoparticles should bind to cells to be detectable.…”

Section: Nanoparticles In Cell Trackingmentioning

confidence: 99%

Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

Dai

Guo

et al. 2021

Nano-Micro Lett.

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Osteoarthritis is the most prevalent chronic and debilitating joint disease, resulting in huge medical and socioeconomic burdens. Intra-articular administration of agents is clinically used for pain management. However, the effectiveness is inapparent caused by the rapid clearance of agents. To overcome this issue, nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic agents. Given the therapeutic programs are inseparable from pathological progress of osteoarthritis, an ideal delivery system should allow the release of therapeutic agents upon specific features of disorders. In this review, we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug release. Then, we review the interactions of nanoparticles with cartilage microenvironment and the rational design. Furthermore, we highlight advances in the therapeutic schemes according to the pathology signals. Finally, armed with an updated understanding of the pathological mechanisms, we place an emphasis on the development of “smart” bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological signals. We anticipate that the exploration of nanoparticles by balancing the efficacy, safety, and complexity will lay down a solid foundation tangible for clinical translation.

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Persistence of fluorescent nanoparticle‐labeled bone marrow mesenchymal stem cells in vitro and after intra‐articular injection

Cited by 10 publications

References 31 publications

Evaluation of Human Skin-Derived Stem Cell Characteristics After Non-Invasive Quantum Dot Labeling

Evaluation of Human Skin-Derived Stem Cell Characteristics After Non-Invasive Quantum Dot Labeling

Comparison of efficacy and safety of single versus repeated intra-articular injection of allogeneic neonatal mesenchymal stem cells for treatment of osteoarthritis of the metacarpophalangeal/metatarsophalangeal joint in horses: A clinical pilot study

Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

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