Effect of Human Umbilical Cord-derived Mesenchymal Stem Cells on Non-cardiac Surgery-induced Lung Injury

Study Overview
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Brief Summary
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This study is an exploratory clinical study to observe the improvement of lung function before and after the treatment by human umbilical cord-derived mesenchymal stem cells, and the purpose is to evaluate the safety and effectiveness of human umbilical cord-derived mesenchymal stem cells on non-cardiac surgery-induced lung injury in patients with ischemic heart disease. The study is a randomized parallel controlled study. Patients receive a review of which main content includes symptom improvement, lung function improvement, and adverse events.

Detailed Description
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This study is an exploratory clinical study to observe the improvement of lung function before and after the treatment by human umbilical cord-derived mesenchymal stem cells, and the purpose is to evaluate the safety and effectiveness of human umbilical cord-derived mesenchymal stem cells on non-cardiac surgery-induced lung injury in patients with ischemic heart disease. The study is a randomized parallel controlled study. The research process is as follows: 1. Sixteen eligible patients with ischemic heart disease were recruited, fully informed, and signed a consent form, and randomly divided into placebo control group (n=8) or hUC-MSCs treatment group (n=8); 2. Knee replacement was performed under general anesthesia in both groups. In the cell therapy group, 1×10^6/kg human umbilical cord-derived mesenchymal stem cells were intravenously injected to the patient immediately after the surgery and at day 3 after the surgery. Before the operation, 6 hours, 3 days, 7days, 14 days, and 28 days after the MSCs injection, all patients receive a review of which main content includes symptom improvement, lung function improvement, and adverse events.

Official Title
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Effect of Human Umbilical Cord-derived Mesenchymal Stem Cells on Non-cardiac Surgery-induced Lung Injury in Patients With Ischemic Heart Disease

Conditions
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Ischemic Heart Disease, Lung Injury, Non-cardiac Surgery

Intervention / Treatment
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* Biological: human umbilical cord-derived mesenchymal stem cells
* Other: saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The electrocardiogram showed T wave change and ST segment depression New York Heart Association (NYHA) Classification of cardiac function Ⅰ-Ⅱ level The patient who first time to receive knee replacement General anesthesia lasted about 2h Signed informed consent Exclusion Criteria: Does not meet the above selection criteria Unable to sign the informed consent Patients with a malignant tumor, other serious systemic diseases, or psychosis Pregnancy, lactation, and those who are not pregnant but do not take effective contraceptives measures The patient with a history of an allergic reaction to biological products or drug The patient has any infectious diseases (including bacterial and viral infections) The patient with cardiac pacemaker implantation within 3 months prior to enrollment The patient who had a stroke within 6 months prior to enrollment Unable to comply with the agreed timetable of this study Patients who are participating in other clinical trials Others who are clinically considered unsuitable for this treatment.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: control<br>In the control group, saline containing 2% albumin (2ml/kg) were intravenously injected to the patient immediately after the surgery and at day 3 after the surgery. | Other: saline<br>* In the control group, saline containing 2% albumin (2ml/kg) were intravenously injected to the patient immediately after the surgery and at day 3 after the surgery.<br>|
| Experimental: MSCs injection<br>In the MSCs injection group, 1×10^6/kg human umbilical cord-derived mesenchymal stem cells were intravenously injected to the patient immediately after the surgery and at day 3 after the surgery. | Biological: human umbilical cord-derived mesenchymal stem cells<br>* In the MSCs injection group, 1×10^6/kg human umbilical cord-derived mesenchymal stem cells were intravenously injected to the patient immediately after the surgery and at day 3 after the surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| oxygenation index | The change in oxygenation index after the operation | Before the operation, 6 hours, 3days, and 7days after the MSCs injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The value of arterial blood cLAC | The change in arterial blood cLAC after the operation | Before the operation and 7days after the MSCs injection | 
| The content of IL-1β | The change in venous blood IL-1β after the operation | Before the operation and 7days after the MSCs injection | 
| The content of IL-6 | The change in venous blood IL-6 after the operation | Before the operation and 7days after the MSCs injection | 
| The content of TGF-α | The change in venous blood TGF-α after the operation | Before the operation and 7days after the MSCs injection | 
| The content of HMGB1 | The change in venous blood HMGB1 after the operation | Before the operation and 7days after the MSCs injection | 
| The content of IL-10 | The change in venous blood IL-10 after the operation | Before the operation and 7days after the MSCs injection | 
| The content of B-type natriuretic peptide (BNP) | The change in venous blood B-type natriuretic peptide after the operation | Before the operation and 7days after the MSCs injection | 
| electrocardiogram | The change in electrocardiogram after the operation | Before the operation, 7days, and 28 days after the MSCs injection | 
| The average length of stay in hospital | The change in the length of stay in hospital between the two groups | The average length of stay in hospital | 
| The visual analog scale（VAS）score | The change in VAS score after the operation，the minimum value is 0 and the maximum value is 10, the higher scores mean a worse outcome. | Before the operation, 6 hours, 3 days, 7days, 14 days, and 28 days after the MSCs injection | 
| The hospital for special surgery (HSS) Knee Score | The change in HSS Knee Score after the operation, the minimum value is 0 and the maximum value is 100, the higher scores mean a better outcome. | Before the operation, 7days, and 28 days after the MSCs injection | 
| The New York Heart Association (NYHA) Functional Classification | The change in NYHA Functional Classification after the operation, the lowest level is Class I and the highest level is Class IV, the higher level mean a worse outcome. | Before the operation, 7days, 14 days, and 28 days after the MSCs injection | 
| The 36-Item Short Form Survey (SF-36) | The change in SF-36 after the operation, the minimum value is 40 and the maximum value is 850, the higher scores mean a better outcome. | Before the operation and 28 days after the MSCs injection | 
| The Hamilton Anxiety Scale | The change in degree of anxiety after the operation, the minimum value is 0 and the maximum value is 56, the higher scores mean a worse outcome. | Before the operation, 7days, 14 days, and 28 days after the MSCs injection | 
| The incidence of allergic reaction | The allergic reaction after the MSCs injection | Before the operation, 6 hours, 3 days, 7days, 14 days, and 28 days after the MSCs injection | 
| The body temperature | The body temperature before and after the operation | Before the operation, 6 hours, 3 days, 7days, 14 days, and 28 days after the MSCs injection | 
| The pulse rate | The pulse rate before and after the operation | Before the operation, 6 hours, 3 days, 7days, 14 days, and 28 days after the MSCs injection | 
| The respiration rate | The respiration rate before and after the operation | Before the operation, 6 hours, 3 days, 7days, 14 days, and 28 days after the MSCs injection | 
| The blood pressure | The blood pressure before and after the operation | Before the operation, 6 hours, 3 days, 7days, 14 days, and 28 days after the MSCs injection | 
| The content of C-reactive protein (CRP) | The change in venous blood CRP after the operation | Before the operation and 7 days after the MSCs injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human umbilical cord-derived mesenchymal stem cells, lung injury