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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">Genes &amp; Cells</journal-id><journal-title-group><journal-title xml:lang="en">Genes &amp; Cells</journal-title><trans-title-group xml:lang="ru"><trans-title>Гены и Клетки</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>Genes and Cells</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2313-1829</issn><issn publication-format="electronic">2500-2562</issn><publisher><publisher-name xml:lang="en">Human Stem Cells Institute</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">633492</article-id><article-id pub-id-type="doi">10.17816/gc633492</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Reviews</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Научные обзоры</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Articular cartilage tissue engineering using genetically modified induced pluripotent stem cell lines</article-title><trans-title-group xml:lang="ru"><trans-title>Применение генетически модифицированных линий индуцированных плюрипотентных стволовых клеток в тканевой инженерии суставного хряща</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0008-3062-5251</contrib-id><name-alternatives><name xml:lang="en"><surname>Gavrilov</surname><given-names>Nikita S.</given-names></name><name xml:lang="ru"><surname>Гаврилов</surname><given-names>Никита Сергеевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>gavrilovns2001@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0008-4421-0495</contrib-id><contrib-id contrib-id-type="spin">9964-2485</contrib-id><name-alternatives><name xml:lang="en"><surname>Ignatyeva</surname><given-names>Nadezda V.</given-names></name><name xml:lang="ru"><surname>Игнатьева</surname><given-names>Надежда Владимировна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci. (Biology)</p></bio><bio xml:lang="ru"><p>канд. биол. наук</p></bio><email>ignateva_n_v_1@staff.sechenov.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6263-0986</contrib-id><contrib-id contrib-id-type="spin">1413-5899</contrib-id><name-alternatives><name xml:lang="en"><surname>Medvedeva</surname><given-names>Ekaterina V.</given-names></name><name xml:lang="ru"><surname>Медведева</surname><given-names>Екатерина Валерьевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci. (Biology)</p></bio><bio xml:lang="ru"><p>канд. биол. наук</p></bio><email>medvedevaekaterina@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7773-2435</contrib-id><contrib-id contrib-id-type="spin">4836-2560</contrib-id><name-alternatives><name xml:lang="en"><surname>Timashev</surname><given-names>Peter S.</given-names></name><name xml:lang="ru"><surname>Тимашев</surname><given-names>Петр Сергеевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci. (Chemistry), Associate Professor</p></bio><bio xml:lang="ru"><p>д-р хим. наук, доцент</p></bio><email>timashev_p_s@staff.sechenov.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">The First Sechenov Moscow State Medical University</institution></aff><aff><institution xml:lang="ru">Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский университет)</institution></aff></aff-alternatives><content-language>ru</content-language><pub-date date-type="preprint" publication-format="electronic" iso-8601-date="2024-10-31"><day>31</day><month>10</month><year>2024</year></pub-date><pub-date date-type="pub" publication-format="electronic" iso-8601-date="2024-12-28"><day>28</day><month>12</month><year>2024</year></pub-date><pub-date date-type="collection"><year>2024</year></pub-date><volume>19</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>404</fpage><lpage>424</lpage><history><date date-type="received" iso-8601-date="2024-06-17"><day>17</day><month>06</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2024-08-28"><day>28</day><month>08</month><year>2024</year></date></history><pub-history><event event-type="received"><event-desc>Received:<date date-type="received" iso-8601-date="2024-06-17"><day>17</day><month>06</month><year>2024</year></date></event-desc></event><event event-type="accepted"><event-desc>Accepted:<date date-type="accepted" iso-8601-date="2024-08-28"><day>28</day><month>08</month><year>2024</year></date></event-desc></event><event event-type="pub"><event-desc>Published:<pub-date date-type="pub" publication-format="electronic" iso-8601-date="2024-12-28"><day>28</day><month>12</month><year>2024</year></pub-date></event-desc></event></pub-history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2024, Эко-Вектор</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2027-12-28"/></permissions><self-uri xlink:href="https://genescells.ru/2313-1829/article/view/633492">https://genescells.ru/2313-1829/article/view/633492</self-uri><abstract xml:lang="en"><p>Mature hyaline cartilage has a low regenerative potential and its repair remains a complex clinical and research issue. Articular cartilage injuries often contribute to the development of osteoarthritis, resulting in loss of joint function and patient disability. Surgical techniques for repairing articular surfaces, such as mosaic chondroplasty and microfracture, which are designed for small defects, cannot be used for degenerative and dystrophic cartilage lesions. Cell therapy using chondrocytes differentiated from induced pluripotent stem cells (iPSCs) is a promising approach to reconstruct articular cartilage tissue. iPSCs have high proliferative activity, which allows the harvesting of autologous cells in quantities necessary to repair a joint defect. CRISPR-Cas genome editing technology, based on the bacterial adaptive immune system, enables the genetic modification of iPSCs to obtain progenitor cells with specific characteristics and properties.</p> <p>This review describes specific research papers on the combined use of iPSC and CRISPR-Cas technologies for the evaluation of cartilage regenerative medicine. Papers were evaluated for the last twelve years since CRISPR-Cas technology was introduced to the global community. CRISPR-Cas is currently being used to address therapeutic issues in articular cartilage regeneration by increasing the efficiency of chondrogenic differentiation of iPSC lines and harvesting a more homogeneous population of chondroprogenitor cells. Another approach is to remove the pro-inflammatory cytokine receptor sequence to produce inflammation-resistant cartilage. Finally, knocking out genes for components of the major histocompatibility complex allows harvesting chondrocytes that are invisible to the recipient's immune system. This kind of research contributes to personalized healthcare and can improve the quality of life of the world's population in the long term.</p></abstract><trans-abstract xml:lang="ru"><p>Зрелый гиалиновый хрящ обладает низким регенеративным потенциалом, и его восстановление на сегодня представляет сложную клиническую и научную проблему. Травмы суставного хряща часто способствуют развитию остеоартрита и, как следствие, потере функциональности сустава и инвалидизации пациентов. Хирургические подходы к восстановлению суставных поверхностей, такие как мозаичная хондропластика и микрофрактурирование, применимые к небольшим размерам дефекта, не могут быть использованы при дегенеративно-дистрофических поражениях хряща. Клеточная терапия с использованием хондроцитов, дифференцированных из индуцированных плюрипотентных стволовых клеток (ИПСК), является перспективным направлением реконструкции тканей суставного хряща. ИПСК обладают высокой пролиферативной активностью, что позволяет получать аутологичные клетки в количестве, которое требуется для восстановления суставного дефекта индивида. Технология редактирования генома CRISPR-Cas, основанная на системе адаптивного иммунитета бактерий, даёт возможность генетически модифицировать ИПСК с целью получения клеток-прогениторов с заданными характеристиками и свойствами.</p> <p>В данном обзоре собраны научные работы узкоспециализированной направленности, посвящённые комбинированию технологий ИПСК и CRISPR-Cas для исследований в области регенеративной медицины хряща. Мы аккумулировали статьи за последние двенадцать лет, с момента, когда метод CRISPR-Cas стал доступным мировому сообществу. Сегодня для решения терапевтических задач в области регенеративной медицины суставного хряща CRISPR-Cas применяется с целью повышения эффективности хондрогенной дифференцировки линий ИПСК и получения более гомогенной популяции хондропрогениторных клеток. Другим походом является удаление последовательности рецепторов провоспалительных цитокинов для получения хрящевой ткани, невосприимчивой к воспалению. Наконец, нокаут генов компонентов главного комплекса гистосовместимости позволяет получать хондроциты, «невидимые» для иммунной системы реципиента. Исследования в данном направлении способствуют развитию персонализированной медицины и в перспективе ведут к повышению качества жизни населения в глобальной популяции.</p></trans-abstract><kwd-group xml:lang="en"><kwd>CRISPR-Cas</kwd><kwd>genome editing</kwd><kwd>articular cartilage</kwd><kwd>chondrocytes</kwd><kwd>hypertrophy</kwd><kwd>induced pluripotent stem cells</kwd><kwd>chondrogenesis</kwd><kwd>regenerative medicine</kwd><kwd>tissue engineering</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>CRISPR-Cas</kwd><kwd>редактирование генома</kwd><kwd>артикулярный хрящ</kwd><kwd>хондроциты</kwd><kwd>гипертрофия</kwd><kwd>индуцированные плюрипотентные стволовые клетки</kwd><kwd>хондрогенез</kwd><kwd>регенеративная медицина</kwd><kwd>тканевая инженерия</kwd></kwd-group><funding-group><funding-statement xml:lang="en">The scientific research was carried out with the support of the Russian Science Foundation (grant No. 21-75-10082).</funding-statement><funding-statement xml:lang="ru">Научное исследование проведено при поддержке Российского научного фонда (грант № 21-75-10082).</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">Kheir E, Shaw D. 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