Allogeneic Transplantation of Expanded Pancreatic Islet Cells

Inclusion Criteria:

1. Voluntarily sign an informed consent form and agree to comply with the trial treatmentplan and visit schedule.
2. Age ≥18 years and ≤60 years on the day of signing the informed consent form,regardless of gender.
3. Body mass index (BMI) ≥18.0 kg/m2 and ≤35.0 kg/m2.
4. Diagnosed with T1DM based on the World Health Organization's diabetes classification (2019).
5. HbA1c ≥7.0% and ≤15.0% at screening.
6. Dependence on insulin injection therapy for ≥5 years, receiving a stable insulintreatment plan for ≥3 months, and injecting insulin three or more times per day orusing an insulin pump.
7. Postprandial mixed meal stimulated C-peptide level <0.3 ng/mL.
8. Experienced impaired awareness of hypoglycemia or significant glycemic instabilityduring screening and in the past 6 months. Hypoglycemic episodes are associated withimpaired awareness of hypoglycemia, extreme glycemic instability, or severe fear andmaladaptive behavior.
9. Sexually active males who are not surgically sterilized or have partners ofchildbearing potential agree to use effective contraception during the entire trialperiod and for at least 6 months after the study ends; sexually active females ofchildbearing potential agree to use effective contraception during the entire studyperiod and for at least 6 months after the study ends.

Exclusion Criteria:

1. Types of diabetes other than T1DM.
2. Body mass index (BMI) >35 kg/m2 or weight <50 kg.
3. Excessive insulin sensitivity and/or insulin resistance (insulin requirement >1.0IU/kg/day or <15 U/day).
4. Previous pancreatic or islet transplantation. Severe trauma, severe infection, orsurgery that may affect glycemic control within one month before screening.
5. History of hypertension with systolic blood pressure (SBP) >160 mmHg and/or diastolicblood pressure (DBP) >100 mmHg after stable dose (at least 4 weeks) ofantihypertensive medication.
6. Blood transfusion or severe bleeding within the past 3 months, knownhemoglobin-related diseases, anemia (moderate to severe), or other knownhemoglobinopathies that interfere with HbA1c measurement (such as sickle celldisease).
7. Impaired liver or kidney function at screening: aspartate aminotransferase (AST) ≥3times the upper limit of normal (ULN), alanine aminotransferase (ALT) ≥3 times ULN,total bilirubin level (TBL) ≥2 times ULN (excluding Gilbert's syndrome), creatinineclearance rate <45 mL/min (calculated by the Cockcroft-Gault formula).
8. Significant albuminuria (urinary albumin excretion rate >300 mg/g) or history thereof.
9. Uncontrolled or untreated thyroid disease or adrenal insufficiency.
10. Severe diabetic kidney disease or renal insufficiency, proliferative retinopathy,diabetic foot ulcers, diabetes-related amputation, and/or severe peripheral neuropathyat screening.
11. Active hepatitis B, hepatitis C, acquired immunodeficiency syndrome, syphilis, ortuberculosis. Even without clinical evidence of active infection, participants withlaboratory evidence of active infection are also excluded.
12. Severe heart disease or a history of cardiovascular disease within 6 months beforescreening, including stroke, decompensated heart failure (NYHA class III or IV),myocardial infarction, unstable angina, or coronary artery bypass grafting.
13. Previous history of coagulation disorders or requiring long-term anticoagulant therapy (e.g., warfarin) (low-dose aspirin therapy is allowed) or patients with INR >1.5.
14. Substance abusers with a history of drug abuse/dependence or drug use within 1 yearbefore screening.
15. Received live vaccines within 14 days before screening or planned to receive livevaccines during the trial or within 1 month after treatment. Live vaccines include,but are not limited to, measles, mumps, rubella, varicella, yellow fever, rabies,Bacillus Calmette-Guérin, typhoid vaccine, COVID-19 vaccine, etc.
16. Patients with a history of acute or chronic pancreatitis, symptomatic gallbladderdisease, pancreatic injury, or other high-risk factors for pancreatitis, or patientswith blood amylase >1.2 times ULN at screening.
17. Other abnormal laboratory test results deemed clinically significant by theinvestigator.
18. Patients with severe mental illness.
19. Participated in a drug or medical device clinical trial within the past 3 months andreceived investigational drugs or medical devices; or within 5 half-lives of anotherdrug before screening (if the half-life exceeds 3 months).
20. Currently receiving long-term (continuous for ≥14 days) systemic pharmacological dosesof glucocorticoids or other medications that may affect the participant'sconsciousness.
21. Treatment (local, intra-articular, intraocular, or inhalation preparations) for anyother factors or diseases not mentioned above, deemed unsuitable for participation inthis clinical study by the investigator.