Human Adipose-Derived Mesenchymal Progenitor Cells Engraft into Rabbit Articular Cartilage

Wang, Wen; He, Na; Feng, Chenchen; Liu, Victor; Zhang, Luyi; Wang, Fei; He, Junxian; Zhu, Tengfang; Wang, Shuyang; Qiao, Weiwei; Li, Suke; Zhou, Guangdong; Zhang, Li; Dai, Chengxiang; Cao, Wei

doi:10.3390/ijms160612076

Cited by 55 publications

(55 citation statements)

References 47 publications

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“…haMSC isolation was described previously [2]. haMSC (1 × 10 6 ; passage 3) were incubated with 10 μM DiD fluorescent dye (Life Technologies & Molecular Probes, USA) for 50 min at 37 °C according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Differentiation of DiD-haMSCs was performed as previously reported [2]. Briefly, for adipogenic and osteogenic differentiation, cells were seeded and grown in StemPro® adipogenesis differentiation medium and StemPro® osteogenesis differentiation medium (Gibco, USA) for 3 weeks, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…In the past decade, the therapeutic potential of mesenchymal stem cells (MSCs) for the treatment of osteoarthritis (OA) has been explored preclinically [1, 2]. The successful preclinical studies have led to the initiation of a number of clinical trials.…”

Section: Introductionmentioning

confidence: 99%

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In vivo human adipose-derived mesenchymal stem cell tracking after intra-articular delivery in a rat osteoarthritis model

Luo

et al. 2016

Stem Cell Res Ther

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BackgroundHuman adipose-derived mesenchymal stem cells (haMSCs) have shown efficacy in treating osteoarthritis (OA) both preclinically and clinically via intra-articular (IA) injection. However, understanding the mode of action of the cell therapy has been limited by cell tracking capability and correlation between the pharmacokinetics of the injected cells and the intended pharmacodynamics effect. This study aims to explore methodology and to understand in vivo biodistribution of clinical-grade haMSCs labeled with fluorescent dye and injected into an immunocompetent OA rat model.MethodshaMSCs labeled with fluorescent dye were investigated for their proliferation and differentiation capabilities. Labeled cells were used to establish detection threshold of a noninvasive biofluorescent imaging system before the cells (2.5 × 106) were injected into a conventional rat OA model induced by medial meniscectomy for 8 weeks. We attempted to reveal the existence of labeled cells in vivo by imaging and a molecular biomarker approach, and to correlate with the in vivo efficacy and physical presence over a follow-up period up to 10 weeks.ResultsIn vitro proliferation and differentiation of haMSCs were not affected by the labeling of DiD dye. Detection thresholds of the labeled cells in vitro and in vivo were determined to be 104 and 105 cells, respectively. When 2.5 × 106 haMSCs were injected into the joints of a rat OA model, fluorescent signals (or >105 cells) lasted for about 10 weeks in the surgical knee joint at the same time as efficacy was observed. Signals in nonsurgical rats only lasted for 4 weeks. The human MSCs were shown to engraft to the rat joint tissues and were proliferative. Human FOXP2 gene was only detected in the knee joint tissue, suggesting limited biodistribution locally to the joints.ConclusionsThe current study represents the first attempt to correlate cell therapy efficacy on OA with the physical presence of the injected haMSCs in the OA model, and demonstrates that human adipose-derived mesenchymal stem cells persisted for 10 weeks locally in the rat joint, coinciding with the efficacy observed. It is postulated that persistence and/or proliferation of the haMSCs in the joint is required in order to exert their functions on promoting joint regeneration and/or cartilage protection, further supporting the safety and feasibility of IA injection of MSCs for the treatment of OA patients.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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In vivo human adipose-derived mesenchymal stem cell tracking after intra-articular delivery in a rat osteoarthritis model

Luo

et al. 2016

Stem Cell Res Ther

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“…The improvement had been observed macroscopically where cartilage lesion had been covered by repaired tissue and the surface was relatively smooth. The histological assessment revealed only a few fissures, few cracks, and an almost continuous superficial zone [85]. Another study showed that injected AMSC migrated to the synovial membrane and meniscus, however not in cartilage.…”

Section: Pre-clinical Studiesmentioning

confidence: 99%

Stem Cell-Based Therapies for Osteoarthritis: From Pre-Clinical to Clinical Applications

Toumi¹,

Lespessailles²,

Mazor³

2017

Mesenchymal Stem Cells - Isolation, Characterization and Applications

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Although many surgical and pharmaceutical interventions are currently available for treating osteoarthritis (OA), restoration of normal cartilage function remains inefficient.In fact, because of the absence of vasculature within the articular cartilage (AC), the selfpotential for regeneration is very poor. Recently, researchers and clinicians have been focusing on alternative methods for cartilage preservation and repair. It has been shown that AC contains a population of stem cells or progenitor cells, similar to those found in many other adult tissues that are thought to be involved in the maintenance of tissue homeostasis. In the present chapter, we review the current status of stem cells potential in the treatment of early OA and discuss the possible origin of these cells and the role they might have in cartilage repair. We also review the recent progress in the field of chondroprogenitors in cartilage.

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“…(24,25) However, many of the cells used in these studies were pretreated with chondrogenic/osteogenic factors, and whether these nonskeletal cells produce functional bone and associated tissues, or whether they induce local cells to undergo a repair process in vivo, (26,27) is not known. (24,25) However, many of the cells used in these studies were pretreated with chondrogenic/osteogenic factors, and whether these nonskeletal cells produce functional bone and associated tissues, or whether they induce local cells to undergo a repair process in vivo, (26,27) is not known.…”

Section: Pluripotent Stem Cells (Embryonic Stem Cells) and Induced Plmentioning

confidence: 99%

American Society for Bone and Mineral Research-Orthopaedic Research Society Joint Task Force Report on Cell-Based Therapies

O’Keefe

Tuan

Lane

et al. 2019

Journal of Bone and Mineral Research

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Cell‐based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell‐based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web‐based marketing and patient testimonials supporting cell‐based therapy. Both the American Society for Bone and Mineral Research (ASBMR) and the Orthopaedic Research Society (ORS) are committed to ensuring that the potential of cell‐based therapies is realized through rigorous, reproducible, and clinically meaningful scientific discovery. The two organizations convened a multidisciplinary and international Task Force composed of physicians, surgeons, and scientists who are recognized experts in the development and use of cell‐based therapies. The Task Force was charged with defining the state‐of‐the art in cell‐based therapies and identifying the gaps in knowledge and methodologies that should guide the research agenda. The efforts of this Task Force are designed to provide researchers and clinicians with a better understanding of the current state of the science and research needed to advance the study and use of cell‐based therapies for skeletal tissues. The design and implementation of rigorous, thorough protocols will be critical to leveraging these innovative treatments and optimizing clinical and functional patient outcomes. In addition to providing specific recommendations and ethical considerations for preclinical and clinical investigations, this report concludes with an outline to address knowledge gaps in how to determine the cell autonomous and nonautonomous effects of a donor population used for bone regeneration. © 2019 American Society for Bone and Mineral Research.

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Human Adipose-Derived Mesenchymal Progenitor Cells Engraft into Rabbit Articular Cartilage

Cited by 55 publications

References 47 publications

In vivo human adipose-derived mesenchymal stem cell tracking after intra-articular delivery in a rat osteoarthritis model

In vivo human adipose-derived mesenchymal stem cell tracking after intra-articular delivery in a rat osteoarthritis model

Stem Cell-Based Therapies for Osteoarthritis: From Pre-Clinical to Clinical Applications

American Society for Bone and Mineral Research-Orthopaedic Research Society Joint Task Force Report on Cell-Based Therapies

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