Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up

for the Cartistem Research Group

doi:10.1177/2325967120973052

Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up

for the Cartistem Research Group

Department of Orthopedic Surgery

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m²), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm² in the UCB-MSC-HA group and 4.0 cm² in the microfracture group (P =.051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group (P =.001); the overall histologic assessment score was also superior in the UCB-MSC-HA group (P =.036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up (P <.05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

Original language	English
Journal	Orthopaedic Journal of Sports Medicine
Volume	9
Issue number	1
DOIs	https://doi.org/10.1177/2325967120973052
State	Published - 2021

Bibliographical note

Funding Information:
One or more of the authors has declared the following potential conflict of interest or source of funding: This study was sponsored and funded by Medipost, the manufacturer of Cartistem. Funding was also received from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI14C3484). B.J.C. has received research support from Aesculap/B.Braun, Arthrex, and Regentis; educational support from Medwest; consulting fees from Acumed, Anika Therapeutics, Arthrex, Bioventus, Flexion Therapeutics, Geistlich Pharma, Regentis, Smith & Nephew, Vericel, and Zimmer Biomet; speaking fees from Arthrex and Lifenet Health; royalties from Arthrex, DJO, Elsevier, and Operative Techniques in Sports Medicine; other financial or material support from Athletico and JRF Ortho; hospitality payments from GE Healthcare; and honoraria from Vericel; and he has stock/stock options in Bandgrip, Ossio, and Regentis. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Publisher Copyright:
© The Author(s) 2021.

Keywords

cartilage restoration
full-thickness cartilage defect
mesenchymal stem cells
microfracture
umbilical cord blood

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@article{0f1149a3a2044007b97d0fe61b0f35a5,

title = "Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up",

abstract = "Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group (P =.051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group (P =.001); the overall histologic assessment score was also superior in the UCB-MSC-HA group (P =.036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up (P <.05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).",

keywords = "cartilage restoration, full-thickness cartilage defect, mesenchymal stem cells, microfracture, umbilical cord blood",

author = "{for the Cartistem Research Group} and Lim, {Hong Chul} and Park, {Yong Beom} and Ha, {Chul Won} and Cole, {Brian J.} and Lee, {Beom Koo} and Jeong, {Hwa Jae} and Kim, {Myung Ku} and Bin, {Seong Il} and Choi, {Chong Hyuk} and Choi, {Choong Hyeok} and Yoo, {Jae Doo} and Yoon, {Jung Ro} and Chung, {Jun Young}",

note = "Funding Information: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was sponsored and funded by Medipost, the manufacturer of Cartistem. Funding was also received from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI14C3484). B.J.C. has received research support from Aesculap/B.Braun, Arthrex, and Regentis; educational support from Medwest; consulting fees from Acumed, Anika Therapeutics, Arthrex, Bioventus, Flexion Therapeutics, Geistlich Pharma, Regentis, Smith & Nephew, Vericel, and Zimmer Biomet; speaking fees from Arthrex and Lifenet Health; royalties from Arthrex, DJO, Elsevier, and Operative Techniques in Sports Medicine; other financial or material support from Athletico and JRF Ortho; hospitality payments from GE Healthcare; and honoraria from Vericel; and he has stock/stock options in Bandgrip, Ossio, and Regentis. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Publisher Copyright: {\textcopyright} The Author(s) 2021.",

year = "2021",

doi = "10.1177/2325967120973052",

language = "English",

volume = "9",

journal = "Orthopaedic Journal of Sports Medicine",

issn = "2325-9671",

publisher = "SAGE Publications Inc.",

number = "1",

}

for the Cartistem Research Group 2021, 'Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up', Orthopaedic Journal of Sports Medicine, vol. 9, no. 1. https://doi.org/10.1177/2325967120973052

Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up. / for the Cartistem Research Group.
In: Orthopaedic Journal of Sports Medicine, Vol. 9, No. 1, 2021.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients

T2 - A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up

AU - for the Cartistem Research Group

AU - Lim, Hong Chul

AU - Park, Yong Beom

AU - Ha, Chul Won

AU - Cole, Brian J.

AU - Lee, Beom Koo

AU - Jeong, Hwa Jae

AU - Kim, Myung Ku

AU - Bin, Seong Il

AU - Choi, Chong Hyuk

AU - Choi, Choong Hyeok

AU - Yoo, Jae Doo

AU - Yoon, Jung Ro

AU - Chung, Jun Young

N1 - Funding Information: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was sponsored and funded by Medipost, the manufacturer of Cartistem. Funding was also received from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI14C3484). B.J.C. has received research support from Aesculap/B.Braun, Arthrex, and Regentis; educational support from Medwest; consulting fees from Acumed, Anika Therapeutics, Arthrex, Bioventus, Flexion Therapeutics, Geistlich Pharma, Regentis, Smith & Nephew, Vericel, and Zimmer Biomet; speaking fees from Arthrex and Lifenet Health; royalties from Arthrex, DJO, Elsevier, and Operative Techniques in Sports Medicine; other financial or material support from Athletico and JRF Ortho; hospitality payments from GE Healthcare; and honoraria from Vericel; and he has stock/stock options in Bandgrip, Ossio, and Regentis. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Publisher Copyright: © The Author(s) 2021.

PY - 2021

Y1 - 2021

N2 - Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group (P =.051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group (P =.001); the overall histologic assessment score was also superior in the UCB-MSC-HA group (P =.036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up (P <.05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

AB - Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group (P =.051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group (P =.001); the overall histologic assessment score was also superior in the UCB-MSC-HA group (P =.036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up (P <.05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

KW - cartilage restoration

KW - full-thickness cartilage defect

KW - mesenchymal stem cells

KW - microfracture

KW - umbilical cord blood

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U2 - 10.1177/2325967120973052

DO - 10.1177/2325967120973052

M3 - Article

AN - SCOPUS:85100163344

SN - 2325-9671

VL - 9

JO - Orthopaedic Journal of Sports Medicine

JF - Orthopaedic Journal of Sports Medicine

IS - 1

ER -