Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes

Frank A Petrigliano; Nancy Q Liu; Siyoung Lee; Jade Tassey; Arijita Sarkar; Yucheng Lin; Liangliang Li; Yifan Yu; Dawei Geng; Jiankang Zhang; Ruzanna Shkhyan; Jacob Bogdanov; Ben Van Handel; Gabriel B Ferguson; Youngjoo Lee; Svenja Hinderer; Kuo-Chang Tseng; Aaron Kavanaugh; J Gage Crump; April D Pyle; Katja Schenke-Layland; Fabrizio Billi; Liming Wang; Jay Lieberman; Mark Hurtig; Denis Evseenko

doi:10.1038/s41536-021-00187-3

Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes

NPJ Regen Med. 2021 Nov 23;6(1):77. doi: 10.1038/s41536-021-00187-3.

Authors

Frank A Petrigliano^#¹, Nancy Q Liu^#¹, Siyoung Lee^#¹, Jade Tassey^#¹, Arijita Sarkar¹, Yucheng Lin^{1

2

3}, Liangliang Li^{1

2

4}, Yifan Yu^{1

2

5}, Dawei Geng^{1

2

6}, Jiankang Zhang^{1

7}, Ruzanna Shkhyan¹, Jacob Bogdanov¹, Ben Van Handel¹, Gabriel B Ferguson¹, Youngjoo Lee¹, Svenja Hinderer⁸, Kuo-Chang Tseng⁹, Aaron Kavanaugh¹⁰, J Gage Crump⁹, April D Pyle^{11

12

13

14}, Katja Schenke-Layland^{8

15

16

17}, Fabrizio Billi¹⁰, Liming Wang², Jay Lieberman¹, Mark Hurtig¹⁸, Denis Evseenko^{19

20}

Affiliations

¹ Department of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, CA, 90033, USA.
² Department of Orthopaedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China.
³ Department of Orthopaedic Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
⁴ Department of Orthopaedics, Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu, 211100, China.
⁵ Department of Orthopaedic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
⁶ Department of Orthopaedic Surgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, 211166, China.
⁷ State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
⁸ The Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany.
⁹ Department of Stem Cell Research and Regenerative Medicine, USC, Los Angeles, CA, 90033, USA.
¹⁰ Department of Orthopaedic Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
¹¹ Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA.
¹² Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA, USA.
¹³ Molecular Biology Institute, UCLA, Los Angeles, CA, USA.
¹⁴ Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA.
¹⁵ Department of Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany.
¹⁶ Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University Tübingen, Tübingen, Germany.
¹⁷ Dept. of Medicine/Cardiology, UCLA, Los Angeles, CA, 90095, USA.
¹⁸ Ontario Veterinary College, Department of Clinical Studies, University of Guelph, Guelph, ON, Canada.
¹⁹ Department of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, CA, 90033, USA. [email protected].
²⁰ Department of Stem Cell Research and Regenerative Medicine, USC, Los Angeles, CA, 90033, USA. [email protected].

^# Contributed equally.

Abstract

Osteoarthritis (OA) impacts hundreds of millions of people worldwide, with those affected incurring significant physical and financial burdens. Injuries such as focal defects to the articular surface are a major contributing risk factor for the development of OA. Current cartilage repair strategies are moderately effective at reducing pain but often replace damaged tissue with biomechanically inferior fibrocartilage. Here we describe the development, transcriptomic ontogenetic characterization and quality assessment at the single cell level, as well as the scaled manufacturing of an allogeneic human pluripotent stem cell-derived articular chondrocyte formulation that exhibits long-term functional repair of porcine articular cartilage. These results define a new potential clinical paradigm for articular cartilage repair and mitigation of the associated risk of OA.

Abstract

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