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  1. Article ; Online: Intermediate-Term Clinical Outcomes of High-Density Autologous Chondrocyte Implantation in Patients with Concomitant Anterior Cruciate Ligament Reconstruction and Focal Chondral Lesions.

    Guillén-Vicente, Isabel / Herros-García, Ramón / Guillén-Vicente, Marta / Ruiz, Borja / Lopez-Alcorocho, Juan Manuel / Rodríguez-Iñigo, Elena / Barrera, Adrián / Fernández-Jaén, Tomás F / Abelow, Steve / Guillén-García, Pedro

    Cartilage

    2024  , Page(s) 19476035241247642

    Abstract: Objective: To investigate intermediate-term clinical results in patients with concomitant anterior cruciate ligament (ACL) reconstruction and chondral defect treated with high-density autologous chondrocyte implantation (HD-ACI) compared to patients ... ...

    Abstract Objective: To investigate intermediate-term clinical results in patients with concomitant anterior cruciate ligament (ACL) reconstruction and chondral defect treated with high-density autologous chondrocyte implantation (HD-ACI) compared to patients without ACL tear but with a chondral lesion and HD-ACI treatment.
    Design: Forty-eight patients with focal chondral lesions underwent HD-ACI (24 with ACL reconstruction after an ACL injury and 24 with an intact ACL). Follow-up assessments occurred at 6, 12, and 24 months. Patient-reported knee function and symptoms were assessed using the International Knee Documentation Committee (IKDC) questionnaire, pain was measured using the Visual Analog Scale (VAS), and adverse events were monitored. Physical activity was assessed using the Tegner Activity Level Scale, and cartilage healing was evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score.
    Results: No significant adverse events occurred during follow-up. Both groups showed significant improvements at 2 years compared to baseline (VAS: 8.0 ± 1.3 to 1.4 ± 2.0 [normal ACL]; 7.4 ± 2.3 to 2.1 ± 2.3 [ACL reconstruction]; IKDC: 39.2 ± 10.6 to 76.1 ± 22.0 [intact ACL]; 35.6 ± 12.1 to 74.6 ± 20.9 [ACL reconstruction]). Patients in both groups exceeded the minimal clinically important difference (MCID) for IKDC scores. The Tegner Activity Level Scale decreased immediately after surgery and increased after 2 years, with 70.6% (normal ACL) and 89.5% (ACL reconstruction) returning to their preinjury activity levels. No significant differences in the MOCART score were observed between the groups.
    Conclusions: ACL reconstruction does not appear to reduce the outcomes (at 2 years) of HD-ACI.
    Language English
    Publishing date 2024-04-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2515870-3
    ISSN 1947-6043 ; 1947-6035
    ISSN (online) 1947-6043
    ISSN 1947-6035
    DOI 10.1177/19476035241247642
    Database MEDical Literature Analysis and Retrieval System OnLINE

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

    Guillén-García, Pedro / Guillén-Vicente, Isabel / Rodríguez-Iñigo, Elena / Guillén-Vicente, Marta / Fernández-Jaén, Tomás Fernando / Navarro, Ramón / Aboli, Lucía / Torres, Raúl / Abelow, Steve / López-Alcorocho, Juan Manuel

    Bioengineering (Basel, Switzerland)

    2023  Volume 10, Issue 9

    Abstract: 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 ... ...

    Abstract 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 cm
    Language English
    Publishing date 2023-09-13
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2746191-9
    ISSN 2306-5354
    ISSN 2306-5354
    DOI 10.3390/bioengineering10091083
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: High-Density Autologous Chondrocyte Implantation as Treatment for Ankle Osteochondral Defects.

    López-Alcorocho, Juan Manuel / Guillén-Vicente, Isabel / Rodríguez-Iñigo, Elena / Navarro, Ramón / Caballero-Santos, Rosa / Guillén-Vicente, Marta / Casqueiro, Mercedes / Fernández-Jaén, Tomás F / Sanz, Fernando / Arauz, Santiago / Abelow, Steve / Guillén-García, Pedro

    Cartilage

    2019  Volume 12, Issue 3, Page(s) 307–319

    Abstract: Purpose: Two-year follow-up to assess efficacy and safety of high-density autologous chondrocyte implantation (HD-ACI) in patients with cartilage lesions in the ankle.: Design: Twenty-four consecutive patients with International Cartilage repair ... ...

    Abstract Purpose: Two-year follow-up to assess efficacy and safety of high-density autologous chondrocyte implantation (HD-ACI) in patients with cartilage lesions in the ankle.
    Design: Twenty-four consecutive patients with International Cartilage repair Society (ICRS) grade 3-4 cartilage lesions of the ankle were included. Five million chondrocytes per cm
    Results: Patients' median age was 31 years (range 18-55 years). Median VAS score was 8 (range 5-10) at baseline, 1.5 (range 0-8) at 12-month follow-up, and 2 (rang e0-5) at 24-month follow-up (
    Conclusion: HD-ACI is a safe and effective technique to treat osteochondral lesions in the talus, providing good clinical and histological results at short- and mid-term follow-ups.
    MeSH term(s) Adolescent ; Adult ; Ankle ; Ankle Joint/surgery ; Chondrocytes ; Humans ; Intra-Articular Fractures ; Middle Aged ; Talus ; Transplantation, Autologous ; Young Adult
    Language English
    Publishing date 2019-03-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2515870-3
    ISSN 1947-6043 ; 1947-6035
    ISSN (online) 1947-6043
    ISSN 1947-6035
    DOI 10.1177/1947603519835898
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Study of Telomere Length in Preimplanted Cultured Chondrocytes.

    López-Alcorocho, Juan Manuel / Guillén-Vicente, Isabel / Rodríguez-Iñigo, Elena / Guillén-Vicente, Marta / Fernández-Jaén, Tomás Fernando / Caballero, Rosa / Casqueiro, Mercedes / Najarro, Pilar / Abelow, Steve / Guillén-García, Pedro

    Cartilage

    2018  Volume 10, Issue 1, Page(s) 36–42

    Abstract: Design: In the process of cell division, the extremes of the eukaryotic chromosomes are progressively shortening, and this phenomenon is related to cell degeneration and senescence. The treatment of cartilage lesions with autologous chondrocytes implies ...

    Abstract Design: In the process of cell division, the extremes of the eukaryotic chromosomes are progressively shortening, and this phenomenon is related to cell degeneration and senescence. The treatment of cartilage lesions with autologous chondrocytes implies that cells proliferate in an artificial environment. We have studied the viability of cultured chondrocytes after measurement of their telomere length before implantation.
    Methods: Articular cartilage biopsies (B1, B2, and B3) were obtained from 3 patients (2 males and 1 female) with knee cartilage defects, who were going to be treated with chondrocyte implantation. Chondrocytes were cultured in DMEM with autologous serum. After the third passage, an aliquot of 1 million cells was removed to estimate the telomere length and the remaining cells were implanted. Telomere length was measured by quantitative fluorescent in situ hybridization (Q-FISH). Patients' clinical outcome was determined preoperatively, and 12 and 24 months postimplantation with the International Knee Documentation Committee (IKDC) questionnaire.
    Results: After chondrocyte implantation, IKDC score doubled at 12 and 24 months with regard to the basal value. After 3 passages, chondrocytes were cultured for a mean of 45.67 days, the mean duplication time being 4.53 days and the mean number of cell divisions being 10.04 during the culture period. The 20th percentile of telomere lengths were 6.84, 6.96, and 7.06 kbp and the median telomere lengths 10.30, 10.47, and 10.73 kbp, respectively. No significant correlation was found between IKDC score and telomere length.
    Conclusion: Culturing autologous chondrocytes for implantation is not related to cell senescence in terms of telomere length.
    MeSH term(s) Adult ; Cartilage Diseases/pathology ; Cartilage Diseases/therapy ; Cartilage, Articular/cytology ; Cartilage, Articular/pathology ; Cells, Cultured ; Chondrocytes/pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Knee Joint/cytology ; Knee Joint/pathology ; Male ; Stem Cell Transplantation ; Telomere/pathology ; Transplantation, Autologous
    Language English
    Publishing date 2018-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2515870-3
    ISSN 1947-6043 ; 1947-6035
    ISSN (online) 1947-6043
    ISSN 1947-6035
    DOI 10.1177/1947603517749918
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cartilage Defect Treatment Using High-Density Autologous Chondrocyte Implantation: Two-Year Follow-up.

    Lopez-Alcorocho, Juan Manuel / Aboli, Lucia / Guillen-Vicente, Isabel / Rodriguez-Iñigo, Elena / Guillen-Vicente, Marta / Fernández-Jaén, Tomás F / Arauz, Santiago / Abelow, Steve / Guillen-García, Pedro

    Cartilage

    2017  Volume 9, Issue 4, Page(s) 363–369

    Abstract: Objective: The aim of this work was to study the short- and mid-term effectiveness and safety of high-density autologous chondrocyte implantation (HD-ACI) in the first 50 patients with knee cartilage damage treated in our unit.: Design: Fifty ... ...

    Abstract Objective: The aim of this work was to study the short- and mid-term effectiveness and safety of high-density autologous chondrocyte implantation (HD-ACI) in the first 50 patients with knee cartilage damage treated in our unit.
    Design: Fifty consecutive patients with cartilage lesions (Outerbridge grade III-IV) in the knee treated with HD-ACI were included in this study. Chondrocytes were isolated from a nonbearing cartilage area biopsy and were cultured until 40 to 50 million cells were obtained. Five million chondrocytes per cm
    Results: The percentage of patients with pain and swelling decreased progressively in the following visits, with differences being statistically significant ( P < 0.001 and P = 0.040, respectively). IKDC scores improved progressively throughout the 24-month follow-up ( P < 0.001). Thus, the mean IKDC score improvement was 26.3 points (95% confidence interval [CI] = 18.2-34.4 points) at 12 months and 31.0 points (95% CI = 22.9-39 points) at 24 months. No significant differences were found when performing extension ( P = 0.112). Flexion significantly improved by 25.1° at 24-month follow-up ( P = 0.013).
    Conclusions: HD-ACI is a safe and effective technique for the treatment of cartilage defects, improving clinical and subjective perception of knee functionality. These preliminary results encourage future studies comparing this technique with traditional ACI.
    MeSH term(s) Adolescent ; Adult ; Animals ; Arthroplasty, Subchondral/methods ; Cartilage Diseases/surgery ; Cartilage, Articular/surgery ; Chondrocytes/transplantation ; Female ; Follow-Up Studies ; Humans ; Knee Joint/surgery ; Male ; Middle Aged ; Prospective Studies ; Swine ; Transplantation, Autologous ; Treatment Outcome ; Young Adult
    Language English
    Publishing date 2017-02-15
    Publishing country United States
    Document type Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2515870-3
    ISSN 1947-6043 ; 1947-6035
    ISSN (online) 1947-6043
    ISSN 1947-6035
    DOI 10.1177/1947603517693045
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Viability of Pathologic Cartilage Fragments as a Source for Autologous Chondrocyte Cultures.

    Guillén-García, Pedro / Rodríguez-Iñigo, Elena / Guillén-Vicente, Isabel / Guillén-Vicente, Marta / Fernández-Jaén, Tomás / Concejero, Vicente / Val, Daniel / Maestro, Antonio / Abelow, Steve / López-Alcorocho, Juan Manuel

    Cartilage

    2016  Volume 7, Issue 2, Page(s) 149–156

    Abstract: Objective: To study if a culture of chondrocytes can be obtained from pathologic hyaline cartilage (PHC) fragments.: Design: Twenty-five men and 9 women with osteochondritis dissecans (OCD) in 11 cases, arthrosis in 13 patients, and trauma in the ... ...

    Abstract Objective: To study if a culture of chondrocytes can be obtained from pathologic hyaline cartilage (PHC) fragments.
    Design: Twenty-five men and 9 women with osteochondritis dissecans (OCD) in 11 cases, arthrosis in 13 patients, and trauma in the remaining 10 cases were included. The PHC fragments and a small sample of the next healthy cartilage were extracted by arthroscopy. According to the appearance, the PHC samples were divided into fixed (3 cases), flapped (6 patients), or loose bodies (25 cases), depending on the attachment degree of the cartilage to the subchondral bone. Approximately half of each pathologic sample and the whole healthy one were digested to isolate the cells trying to establish the cell culture.
    Results: We were able to establish a cell culture in 7 out of 34 (20.6%) PHC samples (positive samples), whereas in the remaining 27 (79.4%) no cell growth was observed (negative samples). Most of the negative samples were loose bodies (P = 0.005) taken from patients with OCD or arthrosis (P = 0.001) with an evolution time of more than 1 year (P < 0.001). The best binary logistic regression model (P < 0.001) showed that the only factor affecting the establishment of cell culture was the evolution time (P = 0.044).
    Conclusion: It is possible to culture chondrocytes from osteochondral fragments if they are traumatic, within a year of injury and not from fragments due to arthrosis or OCD.
    Language English
    Publishing date 2016-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2515870-3
    ISSN 1947-6043 ; 1947-6035
    ISSN (online) 1947-6043
    ISSN 1947-6035
    DOI 10.1177/1947603515621998
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: αKLOTHO and sTGFβR2 treatment counteract the osteoarthritic phenotype developed in a rat model.

    Martinez-Redondo, Paloma / Guillen-Guillen, Isabel / Davidsohn, Noah / Wang, Chao / Prieto, Javier / Kurita, Masakazu / Hatanaka, Fumiyuki / Zhong, Cuiqing / Hernandez-Benitez, Reyna / Hishida, Tomoaki / Lezaki, Takashi / Sakamoto, Akihisa / Nemeth, Amy N / Hishida, Yuriko / Esteban, Concepcion Rodriguez / Shojima, Kensaku / Huang, Ling / Shokhirev, Maxim / Nuñez-Delicado, Estrella /
    Campistol, Josep M / Guillen-Vicente, Isabel / Rodriguez-Iñigo, Elena / Lopez-Alcorocho, Juan Manuel / Guillen-Vicente, Marta / Church, George / Reddy, Pradeep / Guillen-Garcia, Pedro / Liu, Guang-Hui / Belmonte, Juan Carlos Izpisua

    Protein & cell

    2020  Volume 11, Issue 3, Page(s) 219–226

    MeSH term(s) Animals ; Cartilage, Articular/drug effects ; Cartilage, Articular/pathology ; Cell Culture Techniques ; Chondrocytes/drug effects ; Chondrocytes/pathology ; Glucuronidase/therapeutic use ; Humans ; Osteoarthritis, Knee/chemically induced ; Osteoarthritis, Knee/drug therapy ; Papain ; Rats ; Receptor, Transforming Growth Factor-beta Type II/therapeutic use ; Recombinant Proteins/therapeutic use
    Chemical Substances Recombinant Proteins ; Receptor, Transforming Growth Factor-beta Type II (EC 2.7.11.30) ; Glucuronidase (EC 3.2.1.31) ; klotho protein (EC 3.2.1.31) ; Papain (EC 3.4.22.2)
    Language English
    Publishing date 2020-01-16
    Publishing country Germany
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 2543451-2
    ISSN 1674-8018 ; 1674-800X
    ISSN (online) 1674-8018
    ISSN 1674-800X
    DOI 10.1007/s13238-019-00685-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Increasing the Dose of Autologous Chondrocytes Improves Articular Cartilage Repair: Histological and Molecular Study in the Sheep Animal Model.

    Guillén-García, Pedro / Rodríguez-Iñigo, Elena / Guillén-Vicente, Isabel / Caballero-Santos, Rosa / Guillén-Vicente, Marta / Abelow, Stephen / Giménez-Gallego, Guillermo / López-Alcorocho, Juan Manuel

    Cartilage

    2014  Volume 5, Issue 2, Page(s) 114–122

    Abstract: Background: We hypothesized that implanting cells in a chondral defect at a density more similar to that of the intact cartilage could induce them to synthesize matrix with the features more similar to that of the uninjured one.: Methods: We compared ...

    Abstract Background: We hypothesized that implanting cells in a chondral defect at a density more similar to that of the intact cartilage could induce them to synthesize matrix with the features more similar to that of the uninjured one.
    Methods: We compared the implantation of different doses of chondrocytes: 1 million (n = 5), 5 million (n = 5), or 5 million mesenchymal cells (n = 5) in the femoral condyle of 15 sheep. Tissue generated by microfracture at the trochlea, and normal cartilage from a nearby region, processed as the tissues resulting from the implantation, were used as references. Histological and molecular (expression of type I and II collagens and aggrecan) studies were performed.
    Results: The features of the cartilage generated by implantation of mesenchymal cells and elicited by microfractures were similar and typical of a poor repair of the articular cartilage (presence of fibrocartilage, high expression of type I collagen and a low mRNA levels of type II collagen and aggrecan). Nevertheless, in the samples obtained from tissues generated by implantation of chondrocytes, hyaline-like cartilage, cell organization, low expression rates of type I collagen and high levels of mRNA corresponding to type II collagen and aggrecan were observed. These histological features, show less variability and are more similar to those of the normal cartilage used as control in the case of 5 million cells implantation than when 1 million cells were used.
    Conclusions: The implantation of autologous chondrocytes in type I/III collagen membranes at high density could be a promising tool to repair articular cartilage.
    Language English
    Publishing date 2014-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2515870-3
    ISSN 1947-6043 ; 1947-6035
    ISSN (online) 1947-6043
    ISSN 1947-6035
    DOI 10.1177/1947603513515903
    Database MEDical Literature Analysis and Retrieval System OnLINE

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