Chondrocyte Implantation Techniques Research Articles

Autologous chondrocyte implantation for the treatment of osteochondral lesions of the talus: What happens after 20 years?

BackgroundThe purpose of this study was to assess the long-term clinical efficacy of first-generation autologous chondrocyte implantation (ACI) technique for osteochondral lesions of the ankle joint. MethodsEleven patients with symptomatic OLTs underwent ACI from December 1997 to October 2002. A total of 9 patients (5 men, 4 women, age 25.2 ± 6.3) were evaluated at baseline and at 1, 3, 10 years, and at final follow-up of minimum 20 years with AOFAS ankle-hindfoot score, NRS for pain, and with the Tegner score. ResultsThe AOFAS score improved significantly from the baseline value of 40.4 ± 19.8 to 82.7 ± 12.9 at the final follow-up (p < 0.0005). The NRS for pain improved significantly from 7.8 ± 0.7 at baseline to 4.8 ± 2.1 at the final follow-up (p < 0.0005). Moreover, the Tegner score underwent a modification from the pre-operative median value of 1 (range: 1–3) and from a pre-injury value of 5 (range: 3–7) to 3 (range: 2–4) at the final follow-up (p < 0.0005). ConclusionsACI has proven to be an effective treatment option for patients suffering from OLTs, leading to a long-lasting clinical improvement even beyond 20 years of follow-up. Level of evidenceLevel IV

Cartilage Defect Treatment Using High-Density Autologous Chondrocyte Implantation (HD-ACI).

Hyaline cartilage's inability to self-repair can lead to osteoarthritis and joint replacement. Various treatments, including cell therapy, have been developed for cartilage damage. Autologous chondrocyte implantation (ACI) is considered the best option for focal chondral lesions. In this article, we aimed to create a narrative review that highlights the evolution and enhancement of our chondrocyte implantation technique: High-Density-ACI (HD-ACI) Membrane-assisted Autologous Chondrocyte Implantation (MACI) improved ACI using a collagen membrane as a carrier. However, low cell density in MACI resulted in softer regenerated tissue. HD-ACI was developed to improve MACI, implanting 5 million chondrocytes per cm2, providing higher cell density. In animal models, HD-ACI formed hyaline-like cartilage, while other treatments led to fibrocartilage. HD-ACI was further evaluated in patients with knee or ankle defects and expanded to treat hip lesions and bilateral defects. HD-ACI offers a potential solution for cartilage defects, improving outcomes in regenerative medicine and cell therapy. HD-ACI, with its higher cell density, shows promise for treating chondral defects and advancing cartilage repair in regenerative medicine and cell therapy.

Chemically crosslinked hyaluronic acid-chitosan hydrogel for application on cartilage regeneration.

Articular cartilage is an avascular tissue that lines the ends of bones in diarthrodial joints, serves as support, acts as a shock absorber, and facilitates joint's motion. It is formed by chondrocytes immersed in a dense extracellular matrix (principally composed of aggrecan linked to hyaluronic acid long chains). Damage to this tissue is usually associated with traumatic injuries or age-associated processes that often lead to discomfort, pain and disability in our aging society. Currently, there are few surgical alternatives to treat cartilage damage: the most commonly used is the microfracture procedure, but others include limited grafting or alternative chondrocyte implantation techniques, however, none of them completely restore a fully functional cartilage. Here we present the development of hydrogels based on hyaluronic acid and chitosan loaded with chondroitin sulfate by a new strategy of synthesis using biodegradable di-isocyanates to obtain an interpenetrated network of chitosan and hyaluronic acid for cartilage repair. These scaffolds act as delivery systems for the chondroitin sulfate and present mucoadhesive properties, which stabilizes the clot of microfracture procedures and promotes superficial chondrocyte differentiation favoring a true articular cellular colonization of the cartilage. This double feature potentially improves the microfracture technique and it will allow the development of next-generation therapies against articular cartilage damage.

Treatment of Osteochondral Lesions of the Talus With Matrix-induced Autologous Chondrocyte Implantation (MACI)

An osteochondral lesion of the talus is a common injury often resulting from an ankle fracture or ankle sprain. The role of nonoperative management is limited given the diminished healing capacity of these lesions. Among the available surgical options are cell-based techniques, which aim to regenerate hyaline-like articular cartilage. Matrix-induced autologous chondrocyte implantation is one such promising technique that has been validated as an effective and durable treatment option. This article reviews the matrix-induced autologous chondrocyte implantation technique and the evidence supporting its use.

Arthroscopic autologous chondrocyte implantation in the knee with an in situ crosslinking matrix: minimum 4-year clinical results of 15 cases and 1 histological evaluation.

To clinically evaluate an arthroscopic autologous chondrocyte implantation (ACI) technique with an in situ crosslinking matrix for the treatment of full thickness cartilage defects of the knee and to present histological results of a graft cartilage biopsy obtained after 1.5years. Fifteen cases of arthroscopic autologous chondrocyte implantation in the knee performed between November 2011 and October 2012 were included in the study. Medical charts and operational reports were screened and the patients were contacted after 0.8 ± 0.3years (0.4-1.3) and 4.3 ± 0.3years (4.0-4.8) to asses subjective IKDC and re-operation. The Tegner activity scale was collected at the second follow-up time point. Subjective IKDC response rates were assessed at both follow-up time points. The first and second follow-up was completed by all 15 patients (100%). The subjective IKDC scores showed a significant improvement (pre-operative 44.5 ± 15.9, first follow-up 71.1 ± 15.9, p < 0.001, second follow-up 72.6 ± 17.3, p < 0.001). The overall response rate was 66.7% (n = 10) at follow-up one and two. There were no significant differences in pre-injury (4, range 1-9) and follow-up two (4, range 2-7) Tegner activity scales (p = n.s.). Two patients required re-operation in the index knee, not related to the ACI procedure. No complication related to the ACI or the implantation technique occurred. The histological results showed excellent cartilage regeneration. Arthroscopic ACI using an in situ crosslinking matrix is a safe and reliable treatment option for full-thickness cartilage defects of the knee.

Clinical outcome and subchondral bone oedema presence at two-year follow-up after high density autologous chondrocyte implantation treatment in the knee

BackgroundRecently, a new approach of autologous chondrocyte implantation technique (using as biomaterial a collagen type I/III membrane) based on increasing cell density called HD-ACI (high density autologous chondrocyte implantation) has been described. The objective of this paper was to study the clinical outcome and incidence of subchondral bone oedema in patients with cartilage lesions in the knee treated with HD-ACI at 1–2 years of follow-up. MethodsThis is a retrospective study performed with forty patients with chondral injuries grade III-IV. All patients were treated with HD-ACI with a cellular dose of 5×106 chondrocytes/cm2 of lesion. The subjective perception of improvement of symptoms and functionality was measured with the IKDC score (International Knee Documentation Committee). The presence of bone oedema was assessed at 6, 12 and 24 months of follow-up by magnetic resonance imaging. ResultsIKDC values showed a significant improvement at 12 and 24 months (p<.001). The mean difference of IKDC between the baseline visit and 12 months was 26.3 points, and 31.6 points at 24 months. Twenty-seven point five percent of the patients presented subchondral bone oedema at 2 years of follow-up. ConclusionsHD-ACI is an effective and safe treatment that improves pain, clinical perception and functionality of the joint. No correlation was found between the presence of bone oedema and the patients’ clinical outcome.

Evolución clínica y presencia de edema óseo subcondral a los dos años de tratamiento con implante de condrocitos autólogos de alta de densidad en la rodilla

BackgroundRecently, a new approach of autologous chondrocyte implantation technique (using as biomaterial a collagen type i/iii membrane) based on increasing cell density called HD-ACI (High Density Autologous Chondrocyte Implantation) has been described. The objective of this paper was to study the clinical outcome and incidence of subchondral bone oedema in patients with cartilage lesions in the knee treated with HD-ACI at 1-2 years of follow-up. MethodsThis is a retrospective study performed with forty patients with chondral injuries grade iii-iv. All patients were treated with HD-ACI with a cellular dose of 5×106 chondrocytes /cm2 of lesion. The subjective perception of improvement of symptoms and functionality was measured with the IKDC score (International Knee Documentation Committee). The presence of bone oedema was assessed at 6, 12 and 24 months of follow-up by magnetic resonance imaging. ResultsIKDC values showed a significant improvement at 12 and 24 months (P<.001). The mean difference of IKDC between the baseline visit and 12 months was 26.3 points, and 31.6 points at 24 months. Twenty-seven point five percent of the patients presented subchondral bone oedema at 2 years of follow-up. ConclusionsHD-ACI is an effective and safe treatment that improves pain, clinical perception and functionality of the joint. No correlation was found between the presence of bone oedema and the patients’ clinical outcome.

Matrix-Induced Autologous Chondrocyte Implantation With Autologous Bone Grafting for Osteochondral Lesions of the Femoral Trochlea

Matrix-induced autologous chondrocyte implantation is a 2-stage surgical procedure used to treat symptomatic, full-thickness chondral lesions of the knee. This third-generation autologous chondrocyte implantation (ACI) technique improves on the limitations of previous methods, including the risk of uneven chondrocyte distribution at the time of implantation and graft hypertrophy. Given the compliant properties of the scaffold, the graft can be easily shaped to treat irregular chondral defects and applied to articular surfaces with multiplanar geometry (e.g., patella, trochlea). Although ACI techniques are ideally suited to treat chondral surface defects, the ACI “sandwich” technique can be used to treat large osteochondral defects with significant bone loss (>8 mm). Historically, this procedure uses autologous bone graft to replace areas of osseous deficiency along with 2 type I/III collagen bilayer membranes to securely contain the cultured chondrocytes within the defect. We present an analogous technique for the treatment of osteochondral lesions of the femoral trochlea using a single matrix-induced ACI scaffold and autologous bone grafting for a segmental osseous defect.

Transcriptome-Wide Analysis of Human Chondrocyte Expansion on Synoviocyte Matrix.

Human chondrocytes are expanded and used in autologous chondrocyte implantation techniques and are known to rapidly de-differentiate in culture. These chondrocytes, when cultured on tissue culture plastic (TCP), undergo both phenotypical and morphological changes and quickly lose the ability to re-differentiate to produce hyaline-like matrix. Growth on synoviocyte-derived extracellular matrix (SDECM) reduces this de-differentiation, allowing for more than twice the number of population doublings (PD) whilst retaining chondrogenic capacity. The goal of this study was to apply RNA sequencing (RNA-Seq) analysis to examine the differences between TCP-expanded and SDECM-expanded human chondrocytes. Human chondrocytes from three donors were thawed from primary stocks and cultured on TCP flasks or on SDECM-coated flasks at physiological oxygen tension (5%) for 4 passages. During log expansion, RNA was extracted from the cell layer (70–90% confluence) at passages 1 and 4. Total RNA was column-purified and DNAse-treated before quality control analysis and next-generation RNA sequencing. Significant effects on gene expression were observed due to both culture surface and passage number. These results offer insight into the mechanism of how SDECM provides a more chondrogenesis-preserving environment for cell expansion, the transcriptome-wide changes that occur with culture, and potential mechanisms for further enhancement of chondrogenesis-preserving growth.

Combined autologous chondrocyte implantation and meniscus reconstruction for large chondral defect in the lateral compartment due to discoid lateral meniscus tear: A case report.

Discoid lateral meniscus tear leads to large chondral defect in the lateral compartment of the knee joint. There are few effective treatments for large chondral defect in both the tibial and femoral sides with severe degenerative lateral meniscus. We have developed a combined autologous chondrocyte implantation and meniscus reconstruction technique using hamstring tendon. This technique allows biological reconstruction and avoids knee arthroplasty.

Use of Bone Marrow Aspirate Concentrate with Acetabular Labral Repair for the Management of Chondrolabral Junction Breakdown

Despite advances in techniques for acetabular labral repair, strategies for mitigating or reversing damage to the chondrolabral junction do not yet exist. Cartilage repair techniques such as autologous chondrocyte implantation, matrix-induced autologous chondrocyte implantation, osteochondral autograft transfer, microfracture, and bone marrow aspirate concentrate (BMAC) have all been suggested to restore joint congruity and minimize further chondral deterioration. However, chondrocyte implantation techniques and osteochondral grafts are technically challenging in the hip because of its constrained nature, and many cell-based therapies have shown suboptimal results near the chondrolabral junction because of the increased shear forces at the peripheral acetabulum and increased stress at the weight-bearing region of the joint. By using BMAC to augment labral repairs and coat chondrolabral junction breakdown, we are able to introduce mesenchymal stem cells to peripheral acetabular tissue with little to no drawbacks, while avoiding donor-site morbidity, open procedures, and multiple surgeries. The purpose of this Technical Note is to describe a reproducible method for harvesting, processing, and applying BMAC to the chondrolabral surface of the hip during hip arthroscopy without the need for donor-site morbidity or increased labral repair time.

Improvement of the Chondrocyte-Specific Phenotype upon Equine Bone Marrow Mesenchymal Stem Cell Differentiation: Influence of Culture Time, Transforming Growth Factors and Type I Collagen siRNAs on the Differentiation Index.

Articular cartilage is a tissue characterized by its poor intrinsic capacity for self-repair. This tissue is frequently altered upon trauma or in osteoarthritis (OA), a degenerative disease that is currently incurable. Similar musculoskeletal disorders also affect horses and OA incurs considerable economic loss for the equine sector. In the view to develop new therapies for humans and horses, significant progress in tissue engineering has led to the emergence of new generations of cartilage therapy. Matrix-associated autologous chondrocyte implantation is an advanced 3D cell-based therapy that holds promise for cartilage repair. This study aims to improve the autologous chondrocyte implantation technique by using equine mesenchymal stem cells (MSCs) from bone marrow differentiated into chondrocytes that can be implanted in the chondral lesion. The optimized protocol relies on culture under hypoxia within type I/III collagen sponges. Here, we explored three parameters that influence MSC differentiation: culture times, growth factors and RNA interference strategies. Our results suggest first that an increase in culture time from 14 to 28 or 42 days lead to a sharp increase in the expression of chondrocyte markers, notably type II collagen (especially the IIB isoform), along with a concomitant decrease in HtrA1 expression. Nevertheless, the expression of type I collagen also increased with longer culture times. Second, regarding the growth factor cocktail, TGF-β3 alone showed promising result but the previously tested association of BMP-2 and TGF-β1 better limits the expression of type I collagen. Third, RNA interference targeting Col1a2 as well as Col1a1 mRNA led to a more significant knockdown, compared with a conventional strategy targeting Col1a1 alone. This chondrogenic differentiation strategy showed a strong increase in the Col2a1:Col1a1 mRNA ratio in the chondrocytes derived from equine bone marrow MSCs, this ratio being considered as an index of the functionality of cartilage. These data provide evidence of a more stable chondrocyte phenotype when combining Col1a1 and Col1a2 siRNAs associated to a longer culture time in the presence of BMP-2 and TGF-β1, opening new opportunities for preclinical trials in the horse. In addition, because the horse is an excellent model for human articular cartilage disorders, the equine therapeutic approach developed here can also serve as a preclinical step for human medicine.

Chondrogenic potential of IL-10 in mechanically injured cartilage and cellularized collagen ACI grafts.

The application of adjunctive mediators in Autologous chondrocyte implantation (ACI) techniques might be useful for improving the dedifferentiated chondrocyte phenotype, to support neocartilage formation and inhibit post-traumatic cartilage destruction. In this study we examined if (a) interleukin 10 treatment can cause chondrogenic phenotype stabilization and matrix preservation in mechanically injured cartilage and if (b) IL-10 can promote chondrogenesis in a clinically applied collagen scaffold for ACI treatment. For (a) bovine articular cartilage was harvested, subjected to an axial unconfined injury and treated with bovine IL-10 (1-10,000pg/ng/ml). For (b) a post-operatively remaining ACI graft was treated with human IL-10. Expression levels of type I/II/X collagen, SOX9 and aggrecan were measured by qPCR (a,b). After 3 weeks cell death was analyzed (nuclear blebbing and TUNEL assay) and matrix composition was determined by GAG measurements and immunohistochemistry (aggrecan, type I/II collagen, hyaluronic acid). One way ANOVA analysis with Bonferroni's correction. (a) IL-10 stabilized the chondrogenic phenotype after injurious compression and preserved matrix integrity. This was indicated by elevated expression of chondrogenic markers COL2A1, ACAN, SOX9, while COL1A1 and COL10A1 were reduced. An increased GAG content paralleled this and histological staining of type 2 collagen, aggrecan and toluidine blue were enhanced after 3 weeks. (b) IL-10 [100pg/ml] improved the chondrogenic differentiation of human chondrocytes, which was accompanied by cartilaginous matrix formation after 3 weeks of incubation. Interleukin-10 is a versatile adjuvant candidate to control the post-injurious environment in cartilage defects and promote chondrogenesis in ACI grafts.

Characterization and use of Equine Bone Marrow Mesenchymal Stem Cells in Equine Cartilage Engineering. Study of their Hyaline Cartilage Forming Potential when Cultured under Hypoxia within a Biomaterial in the Presence of BMP-2 and TGF-ß1

Articular cartilage presents a poor capacity for self-repair. Its structure-function are frequently disrupted or damaged upon physical trauma or osteoarthritis in humans. Similar musculoskeletal disorders also affect horses and are the leading cause of poor performance or early retirement of sport- and racehorses. To develop a therapeutic solution for horses, we tested the autologous chondrocyte implantation technique developed on human bone marrow (BM) mesenchymal stem cells (MSCs) on horse BM-MSCs. This technique involves BM-MSC chondrogenesis using a combinatory approach based on the association of 3D-culture in collagen sponges, under hypoxia in the presence of chondrogenic factors (BMP-2+TGF-β1) and siRNA to knockdown collagen I and HtrA1. Horse BM-MSCs were characterized before being cultured in chondrogenic conditions to find the best combination to enhance, stabilize, the chondrocyte phenotype. Our results show a very high proliferation of MSCs and these cells satisfy the criteria defining stem cells (pluripotency-surface markers expression). The combination of BMP-2+TGF-β1 strongly induces the chondrogenic differentiation of MSCs and prevents HtrA1 expression. siRNAs targeting Col1a1 and Htra1 were functionally validated. Ultimately, the combined use of specific culture conditions defined here with specific growth factors and a Col1a1 siRNAs (50nM) association leads to the in vitro synthesis of a hyaline-type neocartilage whose chondrocytes present an optimal phenotypic index similar to that of healthy, differentiated chondrocytes. Our results lead the way to setting up pre-clinical trials in horses to better understand the reaction of neocartilage substitute and to carry out a proof-of-concept of this therapeutic strategy on a large animal model.

Tri-layered composite plug for the repair of osteochondral defects: in vivo study in sheep

Cartilage defects are a source of pain, immobility, and reduced quality of life for patients who have acquired these defects through injury, wear, or disease. The avascular nature of cartilage tissue adds to the complexity of cartilage tissue repair or regeneration efforts. The known limitations of using autografts, allografts, or xenografts further add to this complexity. Autologous chondrocyte implantation or matrix-assisted chondrocyte implantation techniques attempt to introduce cultured cartilage cells to defect areas in the patient, but clinical success with these are impeded by the avascularity of cartilage tissue. Biodegradable, synthetic scaffolds capable of supporting local cells and overcoming the issue of poor vascularization would bypass the issues of current cartilage treatment options. In this study, we propose a biodegradable, tri-layered (poly(glycolic acid) mesh/poly(l-lactic acid)-colorant tidemark layer/collagen Type I and ceramic microparticle-coated poly(l-lactic acid)-poly(ϵ-caprolactone) monolith) osteochondral plug indicated for the repair of cartilage defects. The porous plug allows the continual transport of bone marrow constituents from the subchondral layer to the cartilage defect site for a more effective repair of the area. Assessment of the in vivo performance of the implant was conducted in an ovine model (n = 13). In addition to a control group (no implant), one group received the implant alone (Group A), while another group was supplemented with hyaluronic acid (0.8 mL at 10 mg/mL solution; Group B). Analyses performed on specimens from the in vivo study revealed that the implant achieves cartilage formation within 6 months. No adverse tissue reactions or other complications were reported. Our findings indicate that the porous biocompatible implant seems to be a promising treatment option for the cartilage repair.

Chondral defects in the knee: Are autologous bone marrow derived mesenchymal stem cells suitable to replace autologous chondrocyte implantation techniques? results from a mid-term observational cohort study

Chondral defects in the knee: Are autologous bone marrow derived mesenchymal stem cells suitable to replace autologous chondrocyte implantation techniques? results from a mid-term observational cohort study

Repair of partial thickness cartilage defects using cartilage extracellular matrix membrane-based chondrocyte delivery system in human Ex Vivo model.

Treatment options for partial thickness cartilage defects are limited. The purpose of this study was to evaluate the efficacy of the chondrocyte-seeded cartilage extracellular matrix membrane in repairing partial thickness cartilage defects. First, the potential of the membrane as an effective cell carrier was investigated. Secondly, we have applied the chondrocyte-seeded membrane in an ex vivo, partial thickness defect model to analyze its repair potential. After culture of chondrocytes on the membrane in vitro, cell viability assay, cell seeding yield calculation and cell transfer assay were done. Cell carrying ability of the membrane was also tested by seeding different densities of cells. Partial defects were created on human cartilage tissue explants. Cell-seeded membranes were applied using a modified autologous chondrocyte implantation technique on the defects and implanted subcutaneously in nude mice for 2 and 4 weeks. In vitro data showed cell viability and seeding yield comparable to standard culture dishes. Time dependent cell transfer from the membrane was observed. Membranes supported various densities of cells. Ex vivo data showed hyaline-like cartilage tissue repair, integrated on the defect by 4 weeks. Overall, chondrocyte-seeded cartilage extracellular membranes may be an effective and feasible treatment strategy for the repair of partial thickness cartilage defects.

Nuestra experiencia con la técnica de implante de condrocitos autólogos para el tratamiento de lesiones condrales: resultados de 50 pacientes a 2 años de seguimiento

AimThe aim of this work was to evaluate the clinical results of the matrix-induced autologous chondrocyte implantation (MACI) technique on chondral defects of the knee and ankle. A study was conducted on 150 patients treated with MACI (performed by the same team of surgeons in all cases) during 2002-2007. MethodsThe lesion was evaluated by arthroscopy, and a cartilage biopsy was taken. The cellular implant was performed by arthroscopy in 53 patients, and by open surgery in the remaining cases. The results were measured following an in-house clinical protocol. Data corresponding to a mean follow-up period of 24 months were available in 50 out of the 150 implanted patients. Histological studies were performed in a second biopsy taken by arthroscopy in 5 patients 2 years after cell implantation. ResultsIn 89% of patients without previous surgeries, and in 66% of patients with previous surgeries, the results were good or excellent for pain and motion, and most of them were able to return to their previous physical activities, including professional sport. Histological studies performed on a second biopsy showed that the new tissue is hyaline-like cartilage with lower cell numbers and subjectively softer than normal cartilage. ConclusionArthroscopic MACI is a promising procedure to treat chondral lesions in the knee and ankle, although the histological analysis suggests that increasing cellular dosage would improve the results of the technique. Level of evidenceLevel III. Clinical relevanceThe importance of this study is that it presents an increased number of patients with chondral lesion treated with MACI. A high number of these patients were treated with arthroscopic MACI. In the present study it is shown that the treatment gives good results.

Autologous chondrocyte implantation: Is it likely to become a saviour of large-sized and full-thickness cartilage defect in young adult knee?

A literature review of the first-, second- and third-generation autologous chondrocyte implantation (ACI) technique for the treatment of large-sized (>4cm(2)) and full-thickness knee cartilage defects in young adults was conducted, examining the current literature on features, clinical scores, complications, magnetic resonance image (MRI) and histological outcomes, rehabilitation and cost-effectiveness. A literature review was carried out in the main medical databases to evaluate the several studies concerning ACI treatment of large-sized and full-thickness knee cartilage defects in young adults. ACI technique has been shown to relieve symptoms and improve functional assessment in large-sized (>4cm(2)) and full-thickness knee articular cartilage defect of young adults in short- and medium-term follow-up. Besides, low level of evidence demonstrated its efficiency and durability at long-term follow-up after implantation. Furthermore, MRI and histological evaluations provided the evidence that graft can return back to the previous nearly normal cartilage via ACI techniques. Clinical outcomes tend to be similar in different ACI techniques, but with simplified procedure, low complication rate and better graft quality in the third-generation ACI technique. ACI based on the experience of cell-based therapy, with the high potential to regenerate hyaline-like tissue, represents clinical development in treatment of large-sized and full-thickness knee cartilage defects. IV.

Ongoing studies of cell-based therapies for articular cartilage defects in Japan

Ongoing studies of cell-based therapies for articular cartilage defects in Japan Takahiro Ogura,1 Akihiro Tsuchiya,2 Shuichi Mizuno1 1Department of Orthopedic Surgery, Brigham and Women&rsquo;s Hospital and Harvard Medical School, Boston, MA, USA; 2Funabashi Orthopaedic Hospital Sports Medicine Center, Funabashi, Chiba, Japan Abstract: Recently, cell-based therapies have generated great interest in the repair of articular cartilage defects and degeneration. Surgical treatments for these indications have multiple options, including marrow stimulation, osteochondral autograft transplant, and autologous chondrocyte implantation. The autologous chondrocyte implantation technique has been improved using a cell scaffold and other devices. Meanwhile, advanced cell-based therapies, including cultured stem cell treatment, have been studied in clinical trials. Most studies have been designed and authorized by institutional review boards and/or the regulatory agencies of the investigators&rsquo; countries. For cellular products in regenerative medicine, regulations of many countries are amenable to expedited approval. This paper aims to provide an update on ongoing and prospective cell-based therapies, focusing on articular cartilage injury at designated institutions authorized by the Japanese Pharmaceutical and Medical Device Agency. Keywords: autologous chondrocyte implantation, mesenchymal stem cell, knee joint