Cited by 281Pancreatic function and diabetesDiabetes and associated disordersPluripotent Stem Cells Research

The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index; 4 of the 31 sources its claims cite were checked for support.

Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient.

Open access

Wang, Shusen, Du, Yuanyuan, Zhang, Boya, Meng, Gaofan, Liu, Zewen, Liew, Soon Yi, Liang, Rui, Zhang, Zhengyuan, Cai, Xiangheng, Wu, Shuangshuang, Gao, Wei, Zhuang, Dewei, Zou, Jiaqi, Huang, Hui, Wang, Mingyang, Wang, Xiaofeng, Wang, Xuelian, Liang, Ting, Liu, Tengli, Gu, Jiabin, Liu, Na, Wei, Yanling, Ding, Xuejie, Pu, Yue, Zhan, Yixiang, Luo, Yu, Sun, Peng, Xie, Shuangshuang, Yang, Jiuxia, Weng, Yiqi, Zhou, Chunlei, Wang, Zhenglu, Wang, Shuang, Deng, Hongkui, Shen, Zhongyang·2024·Cell

DOI 10.1016/j.cell.2024.09.004

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Abstract

We report the 1-year results from one patient as the preliminary analysis of a first-in-human phase I clinical trial (ChiCTR2300072200) assessing the feasibility of autologous transplantation of chemically induced pluripotent stem-cell-derived islets (CiPSC islets) beneath the abdominal anterior rectus sheath for type 1 diabetes treatment. The patient achieved sustained insulin independence starting 75 days post-transplantation. The patient's time-in-target glycemic range increased from a baseline value of 43.18% to 96.21% by month 4 post-transplantation, accompanied by a decrease in glycated hemoglobin, an indicator of long-term systemic glucose levels at a non-diabetic level. Thereafter, the patient presented a state of stable glycemic control, with time-in-target glycemic range at >98% and glycated hemoglobin at around 5%. At 1 year, the clinical data met all study endpoints with no indication of transplant-related abnormalities. Promising results from this patient suggest that further clinical studies assessing CiPSC-islet transplantation in type 1 diabetes are warranted.

AI snapshot

Written from the paper’s full text.

TL;DR

In a first-in-human phase I trial (ChiCTR2300072200), a 25-year-old woman with 11-year type 1 diabetes received an autologous transplant of chemically induced pluripotent stem-cell-derived islets (CiPSC islets) beneath the abdominal anterior rectus sheath and achieved sustained insulin independence from day 75 post-transplantation. At 1 year, all study endpoints were met with no transplant-related abnormalities detected.

Key findings

The patient achieved complete insulin independence on day 75 and remained insulin-independent through 1 year of follow-up; daily exogenous insulin had been 54 ± 0.9 units/day at baseline.
Time-in-target glycemic range rose from a baseline of 43.18% to 87.18% at month 2 and 96.21% at month 4, and was >98% for 8 months by the 1-year endpoint; HbA1c fell from 7.57% at baseline to 6.50% at day 75 and 5.37% at day 120, remaining in the non-diabetic range (<5.7%) thereafter.
Graft function: fasting C-peptide was undetectable at baseline, rose to 59.6–102.6 pmol/L by week 2, and plateaued at 407.1–721.6 pmol/L after insulin independence; BETA-2 score increased from 0.13 at baseline to 21.42 at day 75 and 41.83 at day 365. OGTT peak C-peptide was 1,847.0, 1,439.9, and 2,472.6 pmol/L at days 180, 270, and 365 (3.5-, 2.8-, and 3.4-fold over fasting).
Safety: no treatment-emergent serious adverse events; treatment-emergent AEs were limited to the peri-transplantation period (puncture-site pain, nausea/vomiting from general anesthesia); no severe hypoglycemic events during follow-up; MRI (T2W-FS and T1W-FS) and tumor markers (β-HCG, AFP, CEA, CA125, CA15-3, CA19-9) showed no evidence of teratoma over 1 year.

Methods

First patient of an ongoing first-in-human phase I trial (TJFCH-iPS-001; ChiCTR2300072200) evaluating safety, tolerability, and efficacy of autologous CiPSC islets in type 1 diabetes; primary endpoints were HbA1c <7.0% or a ≥1% decrease from baseline at 90–365 days, absence of severe hypoglycemic events, and safety/tolerability; secondary endpoints included insulin independence and stimulated C-peptide ≥0.3 ng/mL.
Autologous CiPSCs were generated from the patient's adipose-derived mesenchymal stromal cells by a four-step small-molecule chemical reprogramming protocol (clone CiPSC-#8 selected from 23 colonies), then differentiated via a six-stage protocol into islet-like cells; release testing included dd-PCR for residual PSCs, WGS/WES, viability (98%), CHGA positivity (94.5%), and a glucose stimulation index of 1.37.
1,488,283 IEQ (19,843 IEQ/kg) were injected under ultrasound guidance into the abdominal anterior rectus sheath on June 25, 2023, across 7 injections; the patient continued existing immunosuppression (tacrolimus, mycophenolate mofetil, methylprednisolone) with basiliximab and etanercept induction. Outcomes were tracked by continuous glucose monitoring, HbA1c, C-peptide, OGTT, BETA-2 score, ultrasound/MRI, tumor markers, and autoantibodies.

Limitations

Stated by the paper: safety and efficacy beyond 1 year and in more patients remain to be evaluated; the trial includes three patients total, and data from the second and third patients were not yet mature for reporting, so a larger cohort is warranted.
Stated by the paper: the patient's pre-existing immunosuppression for a transplanted liver precluded evaluation of the recipient's immune response to the autologous graft, limiting insight into potential autoimmune response.
Evident from the text: this is a single-patient report, so no control group or between-patient comparison is possible, and the concurrent immunosuppressive regimen (including basiliximab and etanercept induction) cannot be separated from the graft's contribution to the observed outcomes.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2024.09.004

Cites

72 of 72 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

4 of 31 cited sources checked · 4 supported · 0 flagged

The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Recently, we successfully reprogrammed human somatic cells to chemically induced PSCs (CiPSCs).”
What the sources say
- Not checked — no full text of the sourcecites [4] 4. Guan, J. ∙ Wang, G. ∙ Wang, J. ... Chemical reprogramming of human somatic cells to pluripotent stem cells Nature. 2022; 605:325-331 Crossref Scopus (178) PubMed Google Scholar source
- Supported
  The Results report generating hCiPSCs from human somatic cells obtained from all 17 tested donors. The Results also describe tests confirming that the resulting cells meet the criteria for pluripotent stem cells. (LLM, conf=0.94)
  cites [5] 5. Liuyang, S. ∙ Wang, G. ∙ Wang, Y. ... Highly efficient and rapid generation of human pluripotent stem cells by chemical reprogramming Cell Stem Cell. 2023; 30:450-459.e9 Full Text Full Text (PDF) Scopus (44) PubMed Google Scholar source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
In the paper
“Autologous CiPSCs were induced from adipose-derived mesenchymal stromal cells (ADSCs) isolated from the patient’s adipose tissue by chemical reprogramming as described previously.”
What the sources say
- Not checked — no full text of the sourcecites [4] 4. Guan, J. ∙ Wang, G. ∙ Wang, J. ... Chemical reprogramming of human somatic cells to pluripotent stem cells Nature. 2022; 605:325-331 Crossref Scopus (178) PubMed Google Scholar source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All safety and efficacy clinical endpoints were met at 1-year follow-up of the patient”
- Also stated in: § 1 Send email to zhongyangshen@vip.sina.com … Show more Show less · plain
  “At 1 year, the clinical data met all study endpoints with no indication of transplant-related abnormalities.”
Load-bearingStrength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Within 2 weeks after transplantation, the patient’s daily exogenous insulin dose requirement began to reduce from baseline of 54 ± 0.9 units/day (Figure 2A).”
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.

Show all 75 claims

Probably not a substantial claim. 51
It may state two separate claims as one. 54
The quote only partly states this claim. 2

Every source the paper cites for this claim was checked and supports it.
In the paper
“the generation of CiPSCs from somatic cells employs abiotic, small-molecule chemicals as reprogramming factors that are easily manufactured and standardized, non-genome integrating, scalable, and fine-tunable.”
What the sources say
- Supported
  The Introduction (passage 6; page not provided) describes small-molecule reprogramming factors as abiotic, easily manufactured and standardized, and non-integrative to the genome. It also calls chemical reprogramming suitable for scalable stem-cell generation and describes the process as controllable and tunable (passage 4). (LLM, conf=0.94)
  cites [6] 6. Wang, J. ∙ Sun, S. ∙ Deng, H. Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives Cell Stem Cell. 2023; 30:1130-1147 Full Text Full Text (PDF) Scopus (17) PubMed Google Scholar source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Different from conventional iPSCs, which are generated from somatic cells by genetic overexpression of transcription factors, the generation of CiPSCs from somatic cells employs abiotic, small-molecule chemicals as reprogramming factors”
What the sources say
- Supported
  The Introduction describes conventional iPSC generation through forced expression of defined genes in somatic cells and contrasts TF-induced reprogramming with chemical reprogramming. It explicitly calls small molecules abiotic reprogramming factors and describes CiPSCs produced through chemical reprogramming. No page numbers are available in our copy. (LLM, conf=0.93)
  cites [6] 6. Wang, J. ∙ Sun, S. ∙ Deng, H. Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives Cell Stem Cell. 2023; 30:1130-1147 Full Text Full Text (PDF) Scopus (17) PubMed Google Scholar source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“The small molecules used in the chemical reprogramming approach offer ease of manufacture and standardization and are highly controllable, scalable, and cost-effective, which are important for standardized manufacturing of therapeutic cells.6”
What the sources say
- Supported
  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
  cites [6] 6. Wang, J. ∙ Sun, S. ∙ Deng, H. Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives Cell Stem Cell. 2023; 30:1130-1147 Full Text Full Text (PDF) Scopus (17) PubMed Google Scholar source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the 1-year endpoint, the patient’s TIR had been >98% for 8 months, a substantial improvement in comparison with the baseline TIR of 43.18% (Figure 2C).”
- Also stated in: § Discussion · plain
  “ultimately achieving over 98% blood glucose TIR without exogenous insulin use”
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
In the paper
“Her HbA1c level during the 2 years before enrollment was 7.40%–8.00%, higher than the American Diabetes Association (ADA)’s recommended target for T1D management (<7.0%).”
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [29] 29. American Diabetes Association Professional, Practice Committee
Strength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After insulin independence, the fasting C-peptide reached a plateau and fluctuated within a range of 407.1 to 721.6 pmol/L.”
Load-bearingStrength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After CiPSC-islet transplantation, the patient’s fasting serum C-peptide level, which was undetectable at baseline, increased promptly and reached levels ranging 59.6–102.6 pmol/L by the second week after transplantation (Figure 3A).”
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A TIR of 87.18% was achieved in the patient at month 2 post-transplantation, which increased to 96.21% at month 4 (Figure 2C).”
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
In the paper
“The blood glucose measurement at the 2 h time point was 155 mg/dL, which is below the diagnostic threshold for diabetes (≥200 mg/dL at 2 h).38”
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [38]
Load-bearingStrength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“OGTT tests on days 180, 270, and 365 visits showed peak C-peptide levels of 1,847.0, 1,439.9, and 2,472.6 pmol/L, respectively, while the fold change in peak C-peptide values relative to the fasting C-peptide values was 3.5, 2.8, and 3.4, respectively (Figure 3D).”
Load-bearingStrength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The parallel C-peptide levels were 589.2 pmol/L in the fasting state and peaked at 2 h after glucose administration at 1,436.5 pmol/L, showing a 2.4-fold stimulation (Figure 3D).”
Load-bearingStrength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim. It may state two separate claims as one. The quote only partly states this claim.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The patient’s BETA-2 score increased steadily from a baseline value of 0.13 to 21.42 by the day 75 visit, with the most recent value of 41.83 at day 365 visit (Figure 3E)”
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“From the day 180 visit, the patient’s glucose tolerance showed further improvement, showing relatively stable performance in OGTTs of subsequent visits thereafter (Figures 3B and 3D).”
Load-bearingStrength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the day 120 visit, the meal-responsiveness of C-peptide secretions was further improved, with a fasting level of 407.1 pmol/L and a 2-h postprandial level of 834.1 pmol/L.”
Load-bearingStrength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
In the paper
“We found that transplantation to an extrahepatic site, underneath the abdominal anterior rectus sheath, led to superior CiPSC-islet survival and maturation, resulting in secretion levels of C-peptide (a marker of endogenous insulin secretion) and stimulation indices approaching those of non-diabetic humans.”
What the sources say
- Not checked — no full text of the sourcecites [21] 21. Liang, Z. ∙ Sun, D. ∙ Lu, S. ... Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets Nat. Metab. 2023; 5:29-40 Crossref Scopus (24) PubMed Google Scholar source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“we established a highly efficient, optimized differentiation protocol for the generation of islet-like cells from CiPSCs (CiPSC-islets), whose transcriptomic identity, composition, and insulin secretory function were comparable to that of native human islets.”
What the sources say
- Not checked yetcites [20] 20. Du, Y. ∙ Liang, Z. ∙ Wang, S. ... Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates Nat. Med. 2022; 28:272-282 Crossref Scopus (85) PubMed Google Scholar
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This study was approved by the National Health Commission of the People’s Republic of China and the Medical Ethics Committee at Tianjin First Central Hospital.”
- Also stated in: § Author contributions · plain
  “and was approved by the National Health Commission of the People’s Republic of China and the Medical Ethics Committee at Tianjin First Central Hospital”
Strength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“indicating an increased risk of rejection and graft failure in the case of islet allotransplantation.”
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [31]
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [32]
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [33]
Strength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings supported the viability of CiPSC-islet transplantation underneath the abdominal anterior rectus sheath, which led to relatively rapid restoration of insulin-independent glycemic control in the patient.”
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
In the paper
“The BETA-2 score, which used fasting metabolic variables, was derived and validated by Peter Senior, Shareen Forbes, and colleagues from individuals transplanted in the Edmonton Islet Transplantation Program and is widely used in the clinical assessment of graft function after islet transplantation.”
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [69]
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“while each 1% reduction of HbA1c toward the physiological level has been associated with a 21% reduction in risk of diabetes-related complications and death.52”
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [52]
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Secondly, the use of immunosuppressants in this patient precluded the evaluation of immune response of the recipient to the autologous graft.”
- Also stated in: § Discussion · hedged
  “but insight into potential autoimmune response was limited.”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these findings indicate the feasibility of chemically induced autologous PSCs for cell therapy, constituting a viable personalized medicine strategy.”
Load-bearingStrength:hedged· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
In the paper
“In comparison to intraportal transplantation, the abdominal rectus sheath site also encompasses other safety considerations, such as ease of access for transplantation and imaging and site retention of graft.21”
What the sources say
- Not checked — no full text of the sourcecites [21] 21. Liang, Z. ∙ Sun, D. ∙ Lu, S. ... Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets Nat. Metab. 2023; 5:29-40 Crossref Scopus (24) PubMed Google Scholar source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“For the CiPSC induction, a four step chemical reprogramming protocol without genetic manipulation was applied to patient ADSCs as described previously.4”
What the sources say
- Not checked — no full text of the sourcecites [4] 4. Guan, J. ∙ Wang, G. ∙ Wang, J. ... Chemical reprogramming of human somatic cells to pluripotent stem cells Nature. 2022; 605:325-331 Crossref Scopus (178) PubMed Google Scholar source
Strength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Data from another clinical trial (NCT04786262), which transplanted hPSC-derived islets into the hepatic portal vein, were recently announced, the findings of which also indicated positive outcomes post-transplantation.60”
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [60]
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together with our preclinical studies, the clinical data in this report support the clinical value of this transplantation strategy, warranting continued exploration.”
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibratedSingle case
Tests✓ Asserted: passes? Checkable: unclear✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these results indicated good graft function of the transplanted CiPSC-islets and recovery of endogenous, glucose-responsive insulin secretion in the patient.”
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.

90 of 90

The paper relies on this without support.
The extraperitoneal transplant site has minimal invasiveness of injection and ease of imaging.
“Other important advantages of this self-contained extraperitoneal transplant site include minimal invasiveness of injection at the site and ease of imaging.”
The paper relies on this without support.
The clinical improvements observed after transplantation are attributable to the transplanted CiPSC-islets rather than to other factors such as the immunosuppressive regimen, residual endogenous insulin secretion, or the natural history of the patient’s diabetes.
“After CiPSC-islet transplantation, the patient achieved insulin independence within 3 months post-transplantation, ultimately achieving over 98% blood glucose TIR without exogenous insulin use.”
The paper relies on this without support.
The absence of tumorigenicity observed in mice and nonhuman primates predicts the absence of tumorigenicity in the human patient.
“Prior to the clinical study, the patient CiPSC-islets were assessed in 244 immunodeficient mice in transplantation experiments, with no tumorigenesis observed in all transplanted mice (Table S2).”
The paper relies on this without support.
The patient’s immunosuppressive maintenance regimen did not confound the glycemic or graft-function outcomes attributed to the CiPSC-islet transplant.
“the immunosuppressive maintenance regimen included tacrolimus, mycophenolate mofetil, and methylprednisolone tablets, which were continued after CiPSC transplantation”
The paper relies on this without support.
The abdominal anterior rectus sheath site is safe and effective for stem-cell-derived islet transplantation in humans based on preclinical studies.
“The positive metabolic data seen in this clinical study are consistent with that seen in our preclinical study in nonhuman primates, in which we sought to identify an optimal transplant site for CiPSC-islets.21”
The paper relies on this without support.
Type 1 diabetes is an autoimmune disease.
“Because T1D is an autoimmune disease”

6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

Cryopreserved cells per vial differ between preparation and thawing
Major
The stated cryopreservation concentration and 4 mL aliquot give 1.2 × 10^8 cells per vial, but the thawing procedure says each vial contained 1.8 × 10^8 cells.
Claim of no added immunosuppression conflicts with induction therapy
Minor
The paper says the transplantation did not add to the patient's immunosuppression burden, but it also reports giving basiliximab as induction therapy in addition to her existing maintenance regimen.

2 of 2

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Validation of the BETA-2 Score: An Improved Tool to Estimate Beta Cell Function After Clinical Islet Transplantation Using a Single Fasting Blood Sample
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“20,21 Other important advantages of this transplant site include the circumvention of graft loss from IBMIR.”
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Pluripotent stem-cell-derived therapies in clinical trial: A 2025 update
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Type 2 diabetes mellitus – conventional therapies and future perspectives in innovative treatment
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Progress and challenges in developing allogeneic cell therapies
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“…trial (ChiCTR2300072200) reported autologous transplantation of chemically induced pluripotent stem cell-derived islets beneath the anterior abdominal wall in a patient with type 1 diabetes, achieving insulin independence by day 75 and maintaining glycemic control at one year after transplant 113 .”

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Authors: Wang, S., Du, Y., Zhang, B., Meng, G., Liu, Z., Liew, S. Y., Liang, R., Zhang, Z., Cai, X., Wu, S., Gao, W., Zhuang, D., Zou, J., Huang, H., Wang, M., Wang, X., Wang, X., Liang, T., Liu, T., Gu, J., Liu, N., Wei, Y., Ding, X., Pu, Y., Zhan, Y., Luo, Y., Sun, P., Xie, S., Yang, J., Weng, Y., Zhou, C., Wang, Z., Wang, S., Deng, H., & Shen, Z.
Affiliations: Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Peking University (CN)
Nankai University (CN)
Corresponding author: Wang, Shusen
Deng, Hongkui
Shen, Zhongyang
ORCID: Wang, Shusen
Du, Yuanyuan
Zhang, Boya
Meng, Gaofan
Liew, Soon Yi
Zhang, Zhengyuan
Wu, Shuangshuang
Wang, Xiaofeng
Liang, Ting
Gu, Jiabin
Wei, Yanling
Ding, Xuejie
Xie, Shuangshuang
Weng, Yiqi
Zhou, Chunlei
Deng, Hongkui
Shen, Zhongyang
Venue: Cell
Publisher: Elsevier BV
Published: 2024-10
Volume: 187
Issue: 22
Pages: 6152-6164.e18
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2024.09.004
OpenAlex: W4402843606
Semantic Scholar: 53d12206f7b2371dbe9f6cc2db7448dfa741cad5
Cited by: 281
References: 70
Citations by year: 2026: 120 · 2025: 143 · 2024: 17
FWCI: 117.89
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 395 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (82070805, 32288102, 82100841, NKTM2023002)
Tianjin Municipal Human Resources and Social Security Bureau (XB202011)
Tianjin Municipal Science and Technology Bureau (22JCZXJC00110, 2023C03019)
National Key Research and Development Program of China (2020YFA0803704)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords: type 1 diabetes, islet transplantation, autologous transplantation, anterior rectus sheath, insulin independence, glycemic control, HbA1c
MeSH terms: Single-Case Studies as Topic, Adult, Blood Glucose, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin, Humans, Insulin, Islets of Langerhans, Male, Islets of Langerhans Transplantation, Rectus Abdominis, Induced Pluripotent Stem Cells

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Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient.

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