Effectiveness of Autologous Adipose-derived Stem Cells in the Treatment of Knee Cartilage Injury

Efficacy and Safety Research of Autologous Adipose-derived Mesenchymal Stem Cell Gel in the Treatment of Cartilage Damage in the Knee

This study was aimed to evaluate the efficacy and safety of Autologous Adipose-derived Mesenchymal Stem Cell Gel combine with High tibial osteotomy therapy in the treatment of cartilage damage in the knee. Investigator believe that this method will enable patients to recover better knee function and more repair of knee cartilage.

Study Overview

• Status: Unknown
• Conditions: Knee Osteoarthritis; Cartilage Degeneration
• Intervention / Treatment: Other: Autologous Adipose-derived Mesenchymal Stem Cell Gel; Procedure: Extraction of abdominal fat; Drug: Sodium Hyaluronate

Detailed Description

The patients who will underwent high tibial osteotomy were randomly divided into the experimental group and the control group. Abdominal fat extraction before operation in experimental group to prepare Adipose-derived Mesenchymal Stem Cell Gel, while the control group only underwent high tibial osteotomy. One month after operation, the experimental group was injected with Adipose-derived Mesenchymal Stem Cell Gel into the joint cavity, and the control group was injected with sodium hyaluronate in the joint cavity. Two groups of patients were followed up.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Songlin Li, MD; Phone Number: 0531-82166541; Email: bysonglin@126.com
• Study Contact Backup: Name: Heran Ma, Ph.D; Phone Number: +86 17364590020; Email: 2523129824@qq.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: Heran Ma, Ph.D; Phone Number: +8617364590020; Email: 2523129824@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18-65 years, male and female, patient can tolerate surgery;
• Clinical diagnosis of degenerative arthritis by Radiographic Criteria;
• Obviously extra-articular malformation;
• Good contralateral interventricular cartilage;
• Course of disease ≥ six months;
• There was no obvious abnormality in tumor marker detection,or patient was evaluated has not at the risk of cancer;
• Subjects who understand and sign the consent form for this study.

Exclusion Criteria:

• Acute joint injury;
• Patients with severe primary diseases, such as cardiovascular,cerebrovascular, liver, kidney and hematopoietic system, and psychosis;
• Cancer patients;
• Women who are pregnant or breast feeding,or allergic constitution patient;
• Positive serology for HIV-1 or HIV-2, Hepatitis B (HBsAg, Anti-Hepatitis C virus -Ab), Hepatitis C (Anti-hepatitis C virus -Ab) and syphilis;
• Receive other open surgery related to knee operation within 6 months;
• Participation in another clinical trial;
• Failing to comply with the inclusion criteria, unwilling to comply with the research approach, or incomplete data affecting the curative effect or safety judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous Adipose-derived Mesenchymal Stem Cell Gel; The experimental group received intra-articular injection of Autologous Adipose-derived Mesenchymal Stem Cell Gel one month after operation.	Other: Autologous Adipose-derived Mesenchymal Stem Cell Gel; The experimental group received intra-articular injection of Autologous Adipose-derived Mesenchymal Stem Cell Gel one month after operation.; Procedure: Extraction of abdominal fat; In the experimental group, abdominal fat was extracted before operation to prepare Autologous Adipose-derived Mesenchymal Stem Cell Gel.; Other Names: Fat extraction
Placebo Comparator: sodium hyaluronate; The control group received intra-articular injection of sodium hyaluronate one month after operation.	Drug: Sodium Hyaluronate; The control group received intra-articular injection of sodium hyaluronate one month after operation.; Other Names: hyaluronic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital for special surgery knee score postoperative 1 month	Hospital for special surgery knee score is a knee function scoring system with a full score of 100. 0 means the loss of knee function, 100 means the best knee function, and the greater the value, the better knee function.	postoperative 1 month
Hospital for special surgery knee score postoperative 3 month	Hospital for special surgery knee score is a knee function scoring system with a full score of 100. 0 means the loss of knee function, 100 means the best knee function, and the greater the value, the better knee function.	postoperative 3 month
Hospital for special surgery knee score postoperative 6 month	Hospital for special surgery knee score is a knee function scoring system with a full score of 100. 0 means the loss of knee function, 100 means the best knee function, and the greater the value, the better knee function.	postoperative 6 month
Hospital for special surgery knee score postoperative 12 month	Hospital for special surgery knee score is a knee function scoring system with a full score of 100. 0 means the loss of knee function, 100 means the best knee function, and the greater the value, the better knee function.	postoperative 12 month
Hospital for special surgery knee score postoperative 24 month	Hospital for special surgery knee score is a knee function scoring system with a full score of 100. 0 means the loss of knee function, 100 means the best knee function, and the greater the value, the better knee function.	postoperative 24 month
Hospital for special surgery knee score postoperative 36 month	Hospital for special surgery knee score is a knee function scoring system with a full score of 100. 0 means the loss of knee function, 100 means the best knee function, and the greater the value, the better knee function.	postoperative 36 month
Visual Analogue Scale Postoperative Day 1	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative Day 1
Visual Analogue Scale Postoperative Day 2	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative Day 2
Visual Analogue Scale Postoperative Day 3	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative Day 3
Visual Analogue Scale Postoperative Day 7	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative Day 7
Visual Analogue Scale Postoperative 1 month	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative 1 month
Visual Analogue Scale Postoperative 3 month	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative 3 month
Visual Analogue Scale Postoperative 6 month	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative 6 month
Visual Analogue Scale Postoperative 12 month	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative 12 month
Visual Analogue Scale Postoperative Day One	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative Day One
Visual Analogue Scale Postoperative 24 month	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative 24month
Visual Analogue Scale Postoperative 36 month	Draw a 10 cm horizontal line on the paper. One end of the line is 0, indicating no pain; the other end is 10, indicating severe pain; and the middle part indicates varying degrees of pain. The patient selects a point from the horizontal line and the length from 0 to this point is the Visual Analogue Scale score.	Postoperative 36 month
Evaluation of cartilage repair under MRI postoperative 12 month	Recht criterion was used for grading articular cartilage injury of knee joint, including 0-IV grade, in which: 0 grade, normal articular cartilage, no obvious abnormal signal was found; 1 grade, the layered structure of cartilage disappeared, and there were focal low signal areas, but the surface was smooth; 2 grade, the surface of cartilage was irregular, the depth of cartilage injury was less than 50% cartilage thickness; 3 grade, the surface of cartilage was heavy. The degree of injury is irregular, the depth of injury is more than 50% of the thickness of cartilage or through the whole layer, but the surface of cartilage is not completely exfoliated; Grade IV, full-thickness cartilage defect, articular cartilage injury deep to the cortex, subchondral bone exposed.	Postoperative 12 month
Evaluation of cartilage repair under MRI postoperative 24 month	Recht criterion was used for grading articular cartilage injury of knee joint, including 0-IV grade, in which: 0 grade, normal articular cartilage, no obvious abnormal signal was found; 1 grade, the layered structure of cartilage disappeared, and there were focal low signal areas, but the surface was smooth; 2 grade, the surface of cartilage was irregular, the depth of cartilage injury was less than 50% cartilage thickness; 3 grade, the surface of cartilage was heavy. The degree of injury is irregular, the depth of injury is more than 50% of the thickness of cartilage or through the whole layer, but the surface of cartilage is not completely exfoliated; Grade IV, full-thickness cartilage defect, articular cartilage injury deep to the cortex, subchondral bone exposed.	Postoperative 24 month
Evaluation of cartilage repair under MRI postoperative 36 month	Recht criterion was used for grading articular cartilage injury of knee joint, including 0-IV grade, in which: 0 grade, normal articular cartilage, no obvious abnormal signal was found; 1 grade, the layered structure of cartilage disappeared, and there were focal low signal areas, but the surface was smooth; 2 grade, the surface of cartilage was irregular, the depth of cartilage injury was less than 50% cartilage thickness; 3 grade, the surface of cartilage was heavy. The degree of injury is irregular, the depth of injury is more than 50% of the thickness of cartilage or through the whole layer, but the surface of cartilage is not completely exfoliated; Grade IV, full-thickness cartilage defect, articular cartilage injury deep to the cortex, subchondral bone exposed.	Postoperative 36 month
Degree of meniscus injury under MRI postoperative 12 month	Stoller's criteria were used in the classification of meniscal injuries, including 0-3 grades, in which: 0 grade, the shape of meniscus was regular, complete and even low signal; 1 grade, focal ellipse or circular high signal appeared in the meniscus, which did not extend to the articular surface and margin of the meniscus; 2 grade, the meniscus showed horizontal linear high signal extending to the articular margin of the meniscus. But it did not exceed the articular surface; in grade III, the shape of meniscus was irregular and incomplete. Irregular or linear high signal appeared in the meniscus and extended to the articular surface of meniscus. The grade I and II symptoms of meniscus injury were mild, suggesting meniscus degeneration, and grade III suggesting meniscus tear.	postoperative 12 month
Degree of meniscus injury under MRI postoperative 24 month	Stoller's criteria were used in the classification of meniscal injuries, including 0-3 grades, in which: 0 grade, the shape of meniscus was regular, complete and even low signal; 1 grade, focal ellipse or circular high signal appeared in the meniscus, which did not extend to the articular surface and margin of the meniscus; 2 grade, the meniscus showed horizontal linear high signal extending to the articular margin of the meniscus. But it did not exceed the articular surface; in grade III, the shape of meniscus was irregular and incomplete. Irregular or linear high signal appeared in the meniscus and extended to the articular surface of meniscus. The grade I and II symptoms of meniscus injury were mild, suggesting meniscus degeneration, and grade III suggesting meniscus tear.	postoperative 24 month
Degree of meniscus injury under MRI postoperative 36 month	Stoller's criteria were used in the classification of meniscal injuries, including 0-3 grades, in which: 0 grade, the shape of meniscus was regular, complete and even low signal; 1 grade, focal ellipse or circular high signal appeared in the meniscus, which did not extend to the articular surface and margin of the meniscus; 2 grade, the meniscus showed horizontal linear high signal extending to the articular margin of the meniscus. But it did not exceed the articular surface; in grade III, the shape of meniscus was irregular and incomplete. Irregular or linear high signal appeared in the meniscus and extended to the articular surface of meniscus. The grade I and II symptoms of meniscus injury were mild, suggesting meniscus degeneration, and grade III suggesting meniscus tear.	postoperative 36 month
Evaluation of cartilage repair under arthroscope postoperative 12 month	The arthroscopic classification of knee joint cartilage injury refers to the classification criteria formulated by the International Association of Cartilage Repair, which includes 0-IV grades, of which: 0 grade is normal articular cartilage; 1 grade is the surface injury of cartilage with soft edema on the surface, with only small cracks and intact structure; 2 grade is partial cartilage injury, which extends downward from the surface, but the depth of injury is less than 50% cartilage thickness. Grade III, deep articular injury, injury depth > 50% cartilage thickness or through the whole layer; Grade IV, deep articular cartilage injury to the bone cortex, full-thickness cartilage defect, subchondral bone exposure.	postoperative 12 month
Degree of meniscus injury under arthroscope postoperative 12 month	The degree of meniscus injury under arthroscopy was classified into three grades, including normal, degenerative and tear.	postoperative 12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Squatting to Standing Time postoperative 1 month	The patient squatted on the floor and then stood up completely for five consecutive times, recording the time required.	postoperative 1 month
Squatting to Standing Time postoperative 3 month	The patient squatted on the floor and then stood up completely for five consecutive times, recording the time required.	postoperative 3 month
Squatting to Standing Time postoperative 6 month	The patient squatted on the floor and then stood up completely for five consecutive times, recording the time required.	postoperative 6 month
Squatting to Standing Time postoperative 12 month	The patient squatted on the floor and then stood up completely for five consecutive times, recording the time required.	postoperative 12 month
Squatting to Standing Time postoperative 24 month	The patient squatted on the floor and then stood up completely for five consecutive times, recording the time required.	postoperative 24 month
Squatting to Standing Time postoperative 36 month	The patient squatted on the floor and then stood up completely for five consecutive times, recording the time required.	postoperative 36 month

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University

Publications and helpful links

General Publications

• Baer PC, Geiger H. Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells Int. 2012;2012:812693. doi: 10.1155/2012/812693. Epub 2012 Apr 12.
• Yu D, Xu J, Liu F, Wang X, Mao Y, Zhu Z. Subchondral bone changes and the impacts on joint pain and articular cartilage degeneration in osteoarthritis. Clin Exp Rheumatol. 2016 Sep-Oct;34(5):929-934. Epub 2016 Aug 31.
• Wilusz RE, Sanchez-Adams J, Guilak F. The structure and function of the pericellular matrix of articular cartilage. Matrix Biol. 2014 Oct;39:25-32. doi: 10.1016/j.matbio.2014.08.009. Epub 2014 Aug 27.
• Chareancholvanich K, Pornrattanamaneewong C, Narkbunnam R. Increased cartilage volume after injection of hyaluronic acid in osteoarthritis knee patients who underwent high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc. 2014 Jun;22(6):1415-23. doi: 10.1007/s00167-013-2735-1. Epub 2013 Oct 27.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: May 14, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 20, 2019

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 15, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Knee Osteoarthritis; Stem Cell; Cartilage repair
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: 2018023 (OTHER: Sun Yat-sen University 5010 clinical program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The acquisition of individual participant data needs the consent of Peilai Liu, the person in charge.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No