scholarly journals The clinical potential of articular cartilage-derived progenitor cells: a systematic review

2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Margot Rikkers ◽  
Jasmijn V. Korpershoek ◽  
Riccardo Levato ◽  
Jos Malda ◽  
Lucienne A. Vonk

AbstractOver the past two decades, evidence has emerged for the existence of a distinct population of endogenous progenitor cells in adult articular cartilage, predominantly referred to as articular cartilage-derived progenitor cells (ACPCs). This progenitor population can be isolated from articular cartilage of a broad range of species, including human, equine, and bovine cartilage. In vitro, ACPCs possess mesenchymal stromal cell (MSC)-like characteristics, such as colony forming potential, extensive proliferation, and multilineage potential. Contrary to bone marrow-derived MSCs, ACPCs exhibit no signs of hypertrophic differentiation and therefore hold potential for cartilage repair. As no unique cell marker or marker set has been established to specifically identify ACPCs, isolation and characterization protocols vary greatly. This systematic review summarizes the state-of-the-art research on this promising cell type for use in cartilage repair therapies. It provides an overview of the available literature on endogenous progenitor cells in adult articular cartilage and specifically compares identification of these cell populations in healthy and osteoarthritic (OA) cartilage, isolation procedures, in vitro characterization, and advantages over other cell types used for cartilage repair. The methods for the systematic review were prospectively registered in PROSPERO (CRD42020184775).

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Lu Li ◽  
Yuehui Ma ◽  
Xianglong Li ◽  
Xiangchen Li ◽  
Chunyu Bai ◽  
...  

A chondrocyte progenitor population isolated from the surface zone of articular cartilage has become a promising cell source for cell-based cartilage repair. The cartilage-derived stem/progenitor cells are multipotent stem cells, which can differentiate into three cell types in vitro including adipocytes, osteoblasts, and chondrocytes. Much work has been done on cartilage stem/progenitor cells (CSPCs) from people, horses, and cattle, but the relatively little literature has been published about these cells in chickens. In our work, CSPCs were isolated from chicken embryos in incubated eggs for 20 days. In order to inquire into the biological characteristics of chicken CSPCs, immunofluorescence, reverse transcription-polymerase chain reaction (RT-PCR), and flow cytometry were adopted to detect the characteristic surface markers of CSPCs. Primary CSPCs were subcultured to passage 22 and, for purpose of knowing the change of cell numbers, we drew the growth curves. Isolated CSPCs were induced to adipocytes, osteoblasts, and chondrocytes. Our results suggest that we have identified and characterised a novel cartilage progenitor population resident in chicken articular cartilage and CSPCs isolated from chickens possess similar biological characteristics to those from other species, which will greatly benefit future cell-based cartilage repair therapies.


2021 ◽  
Vol 14 (3) ◽  
pp. 229
Author(s):  
Yo Shinoda ◽  
Daitetsu Kato ◽  
Ryosuke Ando ◽  
Hikaru Endo ◽  
Tsutomu Takahashi ◽  
...  

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Zayed ◽  
Steven Newby ◽  
Nabil Misk ◽  
Robert Donnell ◽  
Madhu Dhar

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.


2020 ◽  
Vol 8 (3) ◽  
pp. 232596712090552 ◽  
Author(s):  
Puwapong Nimkingratana ◽  
Mats Brittberg

Background: The process of returning to work after cartilage treatment has not been studied in depth, even though a better understanding of potential outcomes could lead to significant benefits for the general population. Purpose: To determine which surgical interventions are most effective in helping patients return to work after cartilage repair and to identify factors that affect the ability to return to work. Study Design: Systematic review; Level of evidence, 4. Methods: This systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in analyzing reports on articular cartilage treatment and return to work published from January 1966 (when the first system of classifying articular cartilage injuries based on the mechanism of injuries and type of lesions was developed) to January 2019. General surgical information and available clinical scores were used to assess outcomes. Results: Only 5 studies describing 283 patients were found to be relevant to our objectives and were therefore included in the analysis. Autologous chondrocyte implantation (ACI) and osteochondral allografts were the only 2 procedures for which information was included regarding patient return to work rates. The mean (overall) return-to-work time after a cartilage repair operation was 4.80 ± 3.02 months. ACI was the most common procedure (3 studies; 227 patients). Return to work after ACI or ACI with high tibial osteotomy (HTO) occurred in almost 100% of cases, whereas the rate of return to work was 51.78% for patients who underwent osteochondral allograft ( P < .01); further, patients who had ACI or ACI+HTO returned to work sooner compared with patients who underwent osteochondral allograft. The Knee injury and Osteoarthritis Outcome Score (KOOS) and Single Assessment Numerical Evaluation (SANE) scores were significantly higher in patients who fully returned to work. No significant difference was found in rates of return to work after ACI related to sex, area of the lesion, or size of the defect. Conclusion: The vast majority of published results on articular cartilage repair do not include data on return to work. Although available data on articular cartilage repair in the general population reveal a high rate of return to work, including those patients treated with ACI, the data do not stratify patients by the type and demand of work. No randomized studies have examined return-to-work rates. Hence, authors should include these data in future studies. A refined definition of work intensity, rather than just return to work, may provide a clearer picture of the relative effectiveness of different surgical interventions. To that end, the authors propose a return to work prognostic score called the Prognostic Cartilage Repair Return to Work Score, or PROCART-RTW score.


Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2541-2548 ◽  
Author(s):  
B Herbst ◽  
G Kohler ◽  
A Mackensen ◽  
H Veelken ◽  
P Kulmburg ◽  
...  

We have demonstrated recently that Birbeck granule-positive Langerhans cells (LC) can be derived from CD34+ peripheral blood progenitor cells in the presence of a seven-cytokine cocktail (CC7–7). Here, we show that the sequential use of early-acting hematopoietic growth factors, stem cell factor, interleukin (IL)-3, and IL-6, followed on day 8 by differentiation in the two-factor combination IL-4 plus granulocytemacrophage colony-stimulating factor (GM-CSF) (CC4GM) is more efficient and allows the cells to be arrested in the LC stage for more than 1 week while continuous maturation occurs in CC7–7. Maturation of LC to interdigitating dendritic cells (DC) could specifically be induced within 60 hours by addition of tumor necrosis factor-alpha (20 ng/mL) or lipopolysaccharide (100 ng/mL). Using LC that had been enriched to greater than 90% CD1a+ cells by an immunoaffinity column, we were able to define clear-cut differences between LC and DC that corroborate data of the respective cells derived from epithelial borders (LC) or from lymph nodes (LN) and spleen (DC). Thus, molecules and functions involved in antigen (AG) uptake and processing were highly expressed in LC, while those involved in AG presentation were at maximum in DC. LC were CD1a+2 DR+2, CD23+, CD36+, CD80-, CD86-, and CD25-, while DC were CD1a+/- DR+3, CD23-, CD36-, CD80+, CD86+2, and CD25+, CD40 and CD32 were moderately expressed and nearly unchanged on maturation, in contrast to monocyte-derived DC. Macropinocytosis of fluorescein isothiocyanate-dextran was dominant in LC, as were multilamellar major histocompatibility complex (MHC) class II compartments (MIICs), which were detected by electron microscopy. The functional dichotomy of these cell types was finally supported by testing the AG-presenting cell function for tetanus toxoid to primed autologous T-cell lines, which was optimal when cells were loaded with AG as LC and subsequently induced to become DC.


Cartilage ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Rosa S. Valtanen ◽  
Armin Arshi ◽  
Benjamin V. Kelley ◽  
Peter D. Fabricant ◽  
Kristofer J. Jones

Objective To perform a systematic review of clinical outcomes following microfracture (MFX), autologous chondrocyte implantation (ACI), osteochondral allograft transplantation (OCA), and osteochondral autograft transplantation system (OATS) to treat articular cartilage lesions in pediatric and adolescent patients. We sought to compare postoperative improvements for each cartilage repair method to minimal clinically important difference (MCID) thresholds. Design MEDLINE, Web of Science, Scopus, and Cochrane Library databases were searched for studies reporting MCID-validated outcome scores in a minimum of 5 patients ≤19 years treated for symptomatic knee chondral lesions with minimum 1-year follow-up. One-sample t tests were used to compare mean outcome score improvements to established MCID thresholds. Results Twelve studies reporting clinical outcomes on a total of 330 patients following cartilage repair were identified. The mean age of patients ranged from 13.7 to 16.7 years and the mean follow-up was 2.2 to 9.6 years. Six studies reported on ACI, 4 studies reported on MFX, 2 studies reported on OATS, and 1 study reported on OCA. ACI ( P < 0.001, P = 0.008) and OCA ( P < 0.001) showed significant improvement for International Knee Documentation Committee (IKDC) scores with regard to MCID while MFX ( P = 0.66) and OATS ( P = 0.11) did not. ACI ( P < 0.001) and OATS ( P = 0.010) both showed significant improvement above MCID thresholds for Lysholm scores. MFX ( P = 0.002) showed visual analog scale (VAS) pain score improvement above MCID threshold while ACI ( P = 0.037, P = 0.070) was equivocal. Conclusions Outcomes data on cartilage repair in the pediatric and adolescent knee are limited. This review demonstrates that all available procedures provide postoperative improvement above published MCID thresholds for at least one reported clinical pain or functional outcome score.


2020 ◽  
Vol 8 (8) ◽  
pp. 232596712094531 ◽  
Author(s):  
Matthew J. Kraeutler ◽  
Gianna M. Aliberti ◽  
Anthony J. Scillia ◽  
Eric C. McCarty ◽  
Mary K. Mulcahey

Background: Microfracture (MFx) is one of the most common techniques used for the treatment of articular cartilage defects, although recently there has been a trend toward the use of drilling rather than MFx for the treatment of these defects. Purpose: To perform a systematic review of basic science studies to determine the effect of microfracture versus drilling for articular cartilage repair. Study Design: Systematic review. Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and EMBASE to identify basic science studies comparing outcomes of MFx versus drilling. The search phrase used was microfracture AND (drilling OR microdrilling). Inclusion criteria were basic science studies that directly compared the effect of MFx versus drilling on subchondral bone, bone marrow stimulation, and cartilage regeneration. Results: A total of 7 studies met the inclusion criteria and were included in this systematic review. Of these, 4 studies were performed in rabbits, 1 study in sheep, and 2 studies in humans. All of the included studies investigated cartilage repair in the knee. In the animal studies, microfracture produced fractured and compacted bone and led to increased osteocyte necrosis compared with drilling. Deep drilling (6 mm) was superior to both shallow drilling (2 mm) and MFx in terms of increased subchondral hematoma with greater access to marrow stroma, improved cartilage repair, and increased mineralized bone. However, the overall quality of cartilage repair tissue was poor regardless of marrow stimulation technique. In 2 studies that investigated repair tissue after MFx and/or drilling in human patients with osteoarthritis and cartilage defects, the investigators found that cartilage repair tissue did not achieve the quality of normal hyaline articular cartilage. Conclusion: In the limited basic science studies that are available, deep drilling of cartilage defects in the knee resulted in improved biological features compared with MFx, including less damage to the subchondral bone and greater access to marrow stroma. Regardless of marrow stimulation technique, the overall quality of cartilage regeneration was poor and did not achieve the characteristics of native hyaline cartilage. Overall, there is a general lack of basic science literature comparing microfracture versus drilling for focal chondral defects.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Guillermo Bauza ◽  
Anna Pasto ◽  
Patrick Mcculloch ◽  
David Lintner ◽  
Ava Brozovich ◽  
...  

Abstract Cartilage repair in osteoarthritic patients remains a challenge. Identifying resident or donor stem/progenitor cell populations is crucial for augmenting the low intrinsic repair potential of hyaline cartilage. Furthermore, mediating the interaction between these cells and the local immunogenic environment is thought to be critical for long term repair and regeneration. In this study we propose articular cartilage progenitor/stem cells (CPSC) as a valid alternative to bone marrow-derived mesenchymal stem cells (BMMSC) for cartilage repair strategies after trauma. Similar to BMMSC, CPSC isolated from osteoarthritic patients express stem cell markers and have chondrogenic, osteogenic, and adipogenic differentiation ability. In an in vitro 2D setting, CPSC show higher expression of SPP1 and LEP, markers of osteogenic and adipogenic differentiation, respectively. CPSC also display a higher commitment toward chondrogenesis as demonstrated by a higher expression of ACAN. BMMSC and CPSC were cultured in vitro using a previously established collagen-chondroitin sulfate 3D scaffold. The scaffold mimics the cartilage niche, allowing both cell populations to maintain their stem cell features and improve their immunosuppressive potential, demonstrated by the inhibition of activated PBMC proliferation in a co-culture setting. As a result, this study suggests articular cartilage derived-CPSC can be used as a novel tool for cellular and acellular regenerative medicine approaches for osteoarthritis (OA). In addition, the benefit of utilizing a biomimetic acellular scaffold as an advanced 3D culture system to more accurately mimic the physiological environment is demonstrated.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Soukaina Bahsoun ◽  
Karen Coopman ◽  
Elizabeth C. Akam

AbstractMesenchymal stem cells (MSCs) represent an invaluable asset for the field of cell therapy. Human Bone marrow-derived MSCs (hBM-MSCs) are one of the most commonly used cell types in clinical trials. They are currently being studied and tested for the treatment of a wide range of diseases and conditions. The future availability of MSCs therapies to the public will require a robust and reliable delivery process. Cryopreservation represents the gold standard in cell storage and transportation, but its effect on BM-MSCs is still not well established. A systematic review was conducted to evaluate the impact of cryopreservation on BM-MSCs and to attempt to uncover the reasons behind some of the controversial results reported in the literature. Forty-one in vitro studies were analysed, and their results organised according to the cell attributes they assess. It was concluded that cryopreservation does not affect BM-MSCs morphology, surface marker expression, differentiation or proliferation potential. However, mixed results exist regarding the effect on colony forming ability and the effects on viability, attachment and migration, genomic stability and paracrine function are undefined mainly due to the huge variabilities governing the cryopreservation process as a whole and to the lack of standardised assays.


Sign in / Sign up

Export Citation Format

Share Document