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

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

CiPSC generation is easily manufactured and standardized, non-genome integrating, scalable, and fine-tunable.

“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.”

• 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 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

CiPSCs are generated from somatic cells using abiotic, small-molecule chemicals as reprogramming factors, unlike conventional iPSCs which use genetic overexpression of transcription factors.

“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”

• 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 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

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.

“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”

• 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 sourceSupported

May combine two claims.

The CiPSC-islets were glucose-responsive in vitro, with a glucose stimulation index of 1.37.

“The CiPSC-islets were found to be glucose-responsive in vitro, with a glucose stimulation index of 1.37 (Table S1, part 3).”

May combine two claims.

At the 1-year endpoint, the patient's TIR had been >98% for 8 months, a substantial improvement compared with the baseline TIR of 43.18%.

“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”

• AssumptionRests 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.

May combine two claims.

Transplanted mice showed restoration of glucose tolerance and glucose-responsive C-peptide secretion.

“The transplanted mice also showed restoration of glucose tolerance and glucose-responsive C-peptide secretion (Figures S2G and S2H).”

Probably not a substantial claim: may not pass S3 (load-bearing).

The pancreas graft was removed after a year due to severe thrombotic complications.

“The pancreas graft was removed after a year due to severe thrombotic complications”

May combine two claims.

The patient's HbA1c level during the 2 years before enrollment was 7.40%-8.00%, higher than the ADA recommended target for T1D management (<7.0%).

“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%).”

• cites [29] 29. American Diabetes Association Professional, Practice CommitteeNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The CiPSC-islet preparation had a CHGA-positive proportion of 94.5% of total cells, of which 56.4% were C-peptide and NKX6.1-positive cells.

“and a Chromogranin A (CHGA)-positive proportion of 94.5% of total cells (Figures S3D and S3E), of which 56.4% were C-peptide and NKX6.1-positive cells.”

May combine two claims.

The CiPSC-islet preparation contained 13.4% glucagon-positive cells and 15.9% somatostatin-positive cells.

“The CiPSC-islet preparation also contained 13.4% glucagon-positive cells and 15.9% somatostatin-positive cells, as determined by flow cytometry and immunofluorescence staining (Figures S3D–S3J).”

May combine two claims.

Transplantation experiments showed good survival of patient CiPSC-islets and an absence of teratoma formation or graft overgrowth, including mice observed for up to 58 weeks.

“These transplantation experiments showed good survival of patient CiPSC-islets and an absence of teratoma formation or graft overgrowth (Figures S2A and S2B), including mice observed for an extended period of up to 58 weeks;”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The patient was a 25-year-old woman diagnosed with T1D for 11 years as of transplantation in 2023.

“A 25-year-old woman was diagnosed with T1D for 11 years (as of time of transplantation in 2023).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The patient had two liver transplantations due to cryptogenic cirrhosis in 2014 and 2016, and a whole pancreas transplantation in 2017 due to unstable glycemic control.

“Her medical history included two liver transplantations due to cryptogenic cirrhosis in 2014 and 2016, respectively, and a whole pancreas transplantation in 2017 due to unstable glycemic control.”

May combine two claims.

CGM measurements during the three months before transplantation showed severe glucose variability and endangerment by hypoglycemia.

“Continuous glucose monitoring (CGM) measurements during the three months before transplantation showed severe glucose variability and endangerment by hypoglycemia”

May combine two claims.

Prior to the clinical study, patient CiPSC-islets were assessed in 244 immunodeficient mice in transplantation experiments, with no tumorigenesis observed in all transplanted mice.

“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).”

May combine two claims.

After insulin independence, the patient's fasting C-peptide reached a plateau and fluctuated within a range of 407.1 to 721.6 pmol/L.

“After insulin independence, the fasting C-peptide reached a plateau and fluctuated within a range of 407.1 to 721.6 pmol/L.”

• AssumptionRests 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.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The patient's weight was 75 kg and her body mass index was 27.3 kg/m2.

“Her weight was 75 kg, and her body mass index was 27.3 kg/m2.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The patient was PRA-positive for HLA-I and HLA-II antigens.

“Based on assessments of panel reactive antibodies (PRAs), the patient was found to be PRA-positive for HLA-I and HLA-II antigens”

Probably not a substantial claim: may not pass S3 (load-bearing).

The patient was under regular immunosuppression for liver transplant maintenance.

“The patient was under regular immunosuppression for liver transplant maintenance.”

May combine two claims.

Despite receiving intensive insulin treatment at a daily dose of 54 ± 0.9 units, the patient was still not able to achieve target glycemic control.

“Despite receiving intensive insulin treatment at a daily dose of 54 ± 0.9 units (mean ± SD) under the supervision of an endocrinologist, the patient was still not able to achieve target glycemic control.”

May combine two claims.

After transplantation, the patient's fasting serum C-peptide increased promptly and reached levels ranging 59.6-102.6 pmol/L by the second week after transplantation.

“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).”

• AssumptionRests 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.

May combine two claims.

Single-cell RNA sequencing analysis of the patient CiPSC-islets showed approximately 13% endocrine progenitor cells and approximately 8% enterochromaffin-like cells.

“This was consistent with single-cell RNA sequencing (scRNA-seq) analysis of the patient CiPSC-islets, which also showed ∼13% endocrine progenitor cells and ∼8% enterochromaffin-like cells (Figures S1D–S1F)”

The quote only partly states this claim.

The patient's glycated hemoglobin decreased to a non-diabetic level 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.”

May combine two claims.

The patient's fasting glucose fluctuated greatly, with an average value of 210 ± 59 mg/dL.

“Her fasting glucose fluctuated greatly, with an average value of 210 ± 59 mg/dL (mean ± SD).”

May combine two claims.

A TIR of 87.18% was achieved at month 2 post-transplantation, which increased to 96.21% at month 4.

“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).”

• AssumptionRests 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.

May combine two claims.

In the patient CiPSC-islet preparation, PSC-associated lncRNA transcripts were detected at levels lower than the positive control and similar to the negative control, indicating that residual CiPSCs were not detected.

“The data showed that both transcripts were detected in CiPSC-islets at levels lower than the positive control and similar to the negative control, indicating that residual CiPSCs were not detected.”

May combine two claims.

In this patient, the transplantation area exhibited signal intensities comparable to the surrounding normal muscle tissue (iso-signal), indicating absence of abnormal fat accumulation.

“In this patient, the transplantation area exhibited signal intensities comparable to the surrounding normal muscle tissue (iso-signal), indicating absence of abnormal fat accumulation (Figures 4I–4P).”

May combine two claims.

Before transplantation, the patient suffered from long-term, hard-to-control diabetes complicated by episodes of severe hypoglycemia.

“Before transplantation, the patient suffered from long-term, hard-to-control diabetes complicated by episodes of severe hypoglycemia.”

May combine two claims.

At day 75, 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).

“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”

• cites [38]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• AssumptionRests 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.

May combine two claims.

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.

“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).”

• AssumptionRests 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.

Classified as probably not a substantial claim. May combine two claims. The quote only partly states this claim.

At day 75, 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.

“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).”

• AssumptionRests 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.

May combine two claims.

The patient had previously received a pancreas transplantation in 2017, which had to be removed a year later due to thrombotic complications.

“To improve glycemic control, the patient had previously received a pancreas transplantation in 2017, which had to be removed a year later due to thrombotic complications.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A slight elevation in glutamic acid decarboxylase antibody level at one time point was observed.

“A slight elevation in glutamic acid decarboxylase antibody (GADA) level at one time point was observed.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Karyotype screen of the 23 clones with good morphology and normal cell growth showed abnormal karyotype in one clone, #11, which was removed from downstream screening.

“Karyotype screen of the 23 clones with good morphology and normal cell growth showed abnormal karyotype in one, #11, which was removed from downstream screening.”

May combine two claims.

In this study, good-manufacturing-practice-compliant manufacture of personalized CiPSC-islets for autologous transplantation was conducted, allowing for the first report of clinical transplantation of CiPSC-derived cells.

“In this study, good-manufacturing-practice-compliant manufacture of personalized CiPSC-islets for autologous transplantation was conducted, allowing for the first report of clinical transplantation of CiPSC-derived cells.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Throughout follow-up, the patient was hospitalized one time for an upper respiratory tract infection and was discharged 5 days later.

“Throughout follow-up, the patient was hospitalized one time for an upper respiratory tract infection and was discharged 5 days later.”

May combine two claims.

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.

“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)”

• AssumptionRests 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.

May combine two claims.

Insulin autoantibody, islet cell antibody, insulinoma-associated-2 antibodies, and zinc transporter 8 antibody were consistently negative before and after transplantation.

“Insulin autoantibody (IAA), islet cell antibody (ICA), insulinoma-associated-2 antibodies (IA-2Ab), and zinc transporter 8 antibody (ZnT8) were consistently indicated as negative.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A whole pancreas transplantation was performed on May 4th, 2017, but the pancreas graft was removed one year later (August 8th, 2018) due to thrombotic complications.

“In addition, a whole pancreas transplantation was performed on May 4th, 2017, but the pancreas graft was removed one year later (August 8th, 2018) due to thrombotic complications.”

May combine two claims.

From the day 180 visit, the patient's glucose tolerance showed further improvement, with relatively stable performance in OGTTs of subsequent visits thereafter.

“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).”

• AssumptionRests 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.

May combine two claims.

Treatment-emergent adverse events were limited to the peri-transplantation period, which included pain at the puncture area and nausea and vomiting due to general anesthesia.

“The treatment-emergent AEs were limited to the peri-transplantation period, which included pain at the puncture area and nausea and vomiting due to general anesthesia.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Before CiPSC-islets transplantation, the patient had undergone two liver transplants on July 8th, 2014 and September 27th, 2016, for liver cryptogenic cirrhosis.

“Before CiPSC-islets transplantation, the patient had undergone two liver transplants on July 8th, 2014 and September 27th, 2016, for liver cryptogenic cirrhosis.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The patient CiPSC clone with the highest cell yield was chosen for downstream manufacture (patient CiPSC-#8).

“and the one with the highest cell yield was chosen for downstream manufacture (patient CiPSC-#8).”

May combine two claims.

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.

“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.”

• AssumptionRests 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.

Probably not a substantial claim: may not pass S3 (load-bearing).

The clinical trial's first participant was a 25-year-old female with an 11-year history of T1D.

“In this report, we present data from the clinical trial's first participant—a 25-year-old female with an 11-year history of T1D.”

May combine two claims.

Subsequent T2W-FS images taken over the following 365 days after transplantation showed that the signal of the grafts remained consistent and stable in location, shape, size, and magnetic resonance signal intensity, and the left abdominal rectus exhibited no signs of compression, displacement, or deformation, which together showed no indication of abnormal growth.

“Subsequent T2W-FS images taken over the following 365 days after transplantation showed that the signal of the grafts remained consistent and stable in terms of location, shape, size, and magnetic resonance signal intensity, and the left abdominal rectus exhibited no signs of compression, displacement, or deformation, which together showed no indication of abnormal growth (Figures 4D–4H).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The average temperature during transport was -196.2°C, with highest temperature at -190.7°C and lowest temperature at -196.4°C.

“The average temperature was -196.2°C, with highest temperature at -190.7°C and lowest temperature at -196.4°C respectively.”

May combine two claims.

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 and stimulation indices approaching those of non-diabetic humans.

“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.”

• cites [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 sourceNot checked — no full text of the source

May combine two claims.

A highly efficient, optimized differentiation protocol was established for generation of islet-like cells from CiPSCs (CiPSC-islets), whose transcriptomic identity, composition, and insulin secretory function were comparable to native human islets.

“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.”

• cites [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 ScholarNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

In-process quality control (QC) assessments were performed throughout the manufacturing process.

“with in-process quality control (QC) assessments throughout the manufacturing process.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The 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.

“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”

Probably not a substantial claim: may not pass S3 (load-bearing).

PRA positivity for HLA-I and HLA-II antigens indicates an increased risk of rejection and graft failure in the case of islet allotransplantation.

“indicating an increased risk of rejection and graft failure in the case of islet allotransplantation.”

• 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]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The patient CiPSC-islet manufacturing process was subject to in-process quality controls.

“The patient CiPSC-islet manufacturing process was subject to in-process QCs as shown in Table S1, part 2.”

Classified as probably not a substantial claim.

The selected patient CiPSC line used for downstream manufacture (patient CiPSC-#8) was systematically characterized, including trilineage differentiation potential and genomic stability assays.

“Systematic characterization of the selected patient CiPSC line used for downstream manufacture (patient CiPSC-#8) was performed, including trilineage differentiation potential and genomic stability assays.”

May combine two claims.

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.

“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.”

• AssumptionRests 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.

Classified as probably not a substantial claim.

In vivo tumorigenicity tests prior to clinical transplantation of patient CiPSC-islets were performed on 50 immunodeficient SCID/Beige mice.

“In vivo tumorigenicity tests prior to clinical transplantation of patient CiPSC-islets were performed on 50 immunodeficient SCID/Beige mice.”

May combine two claims.

In this study, an extrahepatic site was employed, which was a favorable option for this patient on account of her transplanted liver.

“In this study, an extrahepatic site was employed, which was a favorable option for this patient on account of her transplanted liver.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Non-synonymous mutations identified in the patient's ADSCs, CiPSC line, and patient's CiPSC-islets were evaluated for pathogenicity and/or carcinogenicity by screening against COSMIC Census, COSMIC, and Clinvar databases.

“Non-synonymous mutations identified were shown below. The pathogenicity and/or carcinogenicity of these mutations was evaluated by screening of each genomic variants against the COSMIC Census, and their status in COSMIC databases and Clinvar databases, if any, was annotated in the right two columns.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Viability and yield of CiPSC-islet cells were verified by trypan blue and Countess II Automated Cell Counter.

“Viability and yield were verified by trypan blue (Invitrogen, T10282) and Countess II Automated Cell Counter (Invitrogen, AMQAX1000).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The BETA-2 score, which uses 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.

“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.”

• cites [69]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim. May combine two claims.

Safety and efficacy of CiPSC-islet transplantation beyond 1 year and in more than one patient remain to be evaluated.

“Firstly, safety and efficacy beyond 1 year and in more patients remain to be evaluated.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Each 1% reduction of HbA1c toward the physiological level has been associated with a 21% reduction in risk of diabetes-related complications and death.

“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”

• cites [52]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The second and third patients were sequentially enrolled in accordance with regulatory safety requirements.

“Follow-up with these patients is ongoing, as they were sequentially enrolled in accordance with regulatory safety requirements.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study was conducted in accordance with the Clinical Study Protocol.

“and was conducted in accordance to the Clinical Study Protocol (Data S1).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Whole-genome sequencing and whole-exome sequencing data were generated for the patient's ADSCs, CiPSC line, and the patient's CiPSC-islets.

“Whole-genome sequencing data and whole-exome sequencing data (WGS and WES) were generated for the patient’s ADSCs, CiPSC line, and the patient’s CiPSC-islets.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Flow cytometry was performed in dissociated cells for islet endocrine cell-related markers (NKX6.1, C-peptide, GCG, SST).

“Flow cytometry was performed in dissociated cells for islet endocrine cell-related markers (NKX6.1, C-peptide, GCG, SST).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Before transplantation, the items in Quality control and final check of CiPSC-islets preparation (Table S1 Part 3) were tested as a final check.

“During this time before transplantation, the items in Quality control and final check of CiPSC-islets preparation before transplantation (as shown in Table S1 Part 3) were tested as a final check.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The current patient provided written informed consent to undergo the procedure.

“The current patient provided written informed consent to undergo the procedure.”

May combine two claims.

The use of immunosuppressants in this patient precluded the evaluation of the immune response of the recipient to the autologous graft, including potential autoimmune response.

“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.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Data from the second and third patients are not yet matured for reporting due to the limited follow-up period and according to the clinical trial protocol.

“However, due to the limited follow-up period and according to our clinical trial protocol, data from these two patients are not yet matured for reporting.”

May combine two claims.

Taken together, these findings indicate the feasibility of chemically induced autologous PSCs for cell therapy, constituting a viable personalized medicine strategy.

“Taken together, these findings indicate the feasibility of chemically induced autologous PSCs for cell therapy, constituting a viable personalized medicine strategy.”

• AssumptionRests 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.

Classified as probably not a substantial claim.

Glucose stimulated insulin secretion (GSIS) assay was conducted to evaluate the Glucose Stimulation Index (GSI) of functional potency.

“Glucose stimulated insulin secretion (GSIS) assay was conducted to evaluate the Glucose Stimulation Index (GSI) of functional potency.”

May combine two claims.

In comparison to intraportal transplantation, the abdominal rectus sheath site encompasses other safety considerations, such as ease of access for transplantation and imaging and site retention of graft.

“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”

• cites [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 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The CiPSC induction protocol used for patient ADSCs did not involve genetic manipulation.

“For the CiPSC induction, a four step chemical reprogramming protocol without genetic manipulation was applied to patient ADSCs as described previously.4”

• cites [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 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Viability of CiPSC-islets was tested by fluorescein diacetate (FDA) / propidium iodide (PI) staining.

“the viability of CiPSC-islets was tested by fluorescein diacetate (FDA) / propidium iodide (PI) staining.”

Probably not a substantial claim: may not pass S3 (load-bearing).

CiPSC-islet cell recovery and preparation was conducted at the clinical site under GMP-level conditions.

“CiPSC-islet cell recovery and preparation was conducted at the clinical site under GMP-level conditions.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The clinical trial is ongoing and includes three patients in total.

“The trial is ongoing and includes three patients in total.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Data from another clinical trial (NCT04786262), which transplanted hPSC-derived islets into the hepatic portal vein, indicated positive outcomes post-transplantation.

“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”

• cites [60]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Short tandem repeat (STR), whole genome sequencing (WGS) and whole exome sequencing (WES) tests were conducted on the selected clone #8, which passed all the tests.

“Short tandem repeat (STR), whole genome sequencing (WGS) and whole exome sequencing (WES) tests were conducted on the selected clone #8, which passed all the tests.”

May combine two claims.

Taken together with the preclinical studies, the clinical data in this report support the clinical value of this transplantation strategy, warranting continued exploration.

“Taken together with our preclinical studies, the clinical data in this report support the clinical value of this transplantation strategy, warranting continued exploration.”

• AssumptionRests 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.

Probably not a substantial claim: may not pass S3 (load-bearing).

The patient CiPSC-#8 cell line was assessed for quality according to the requirements in Table S1 Part 1.

“The patient CiPSC-#8 cell line was assessed for quality according to the requirements in Table S1 Part 1.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study was conducted in accordance with the Declaration of Helsinki.

“The study was conducted in accordance with the Declaration of Helsinki”

Classified as probably not a substantial claim.

Thorough testing of the final CiPSC-islets was conducted to detect for residues of concern, including residual BSA and cytokines.

“Thorough testing of the final CiPSC-islets was conducted to detect for residues of concern, including residual BSA and cytokines.”

May combine two claims.

Pre-transplantation C-peptide measures were undetectable, indicating a complete destruction of β cells and poor glucose tolerance.

“C-peptide measures taken in parallel showed undetectable C-peptide levels (Figure 3D), indicating a complete destruction of β cells and poor glucose tolerance.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Mycoplasma contamination, sterility and endotoxin levels were checked according to protocols in the Chinese pharmacopoeia (2020 version).

“In addition, mycoplasma contamination, sterility and endotoxin levels were checked according to protocols in the Chinese pharmacopoeia (2020 version).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The reagents used in the entire manufacturing process were subject to reagent controls, including checking documentation of certificates of analysis (COA) of every reagent.

“The reagents used in the entire manufacturing process was subject to reagent controls, including checking documentation of certificates of analysis (COA) of every reagent.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Prior to the start of patient recruitment, the trial was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300072200).

“Prior to the start of patient recruitment, the trial was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300072200).”

Classified as probably not a substantial claim.

Droplet digital PCR (dd-PCR) was performed to verify biosafety of patient CiPSCs-islets.

“We performed droplet digital PCR (dd-PCR) to verify biosafety of patient CiPSCs-islets.”

May combine two claims.

Taken together, the results indicated good graft function of the transplanted CiPSC-islets and recovery of endogenous, glucose-responsive insulin secretion in the patient.

“Taken together, these results indicated good graft function of the transplanted CiPSC-islets and recovery of endogenous, glucose-responsive insulin secretion in the patient.”

• AssumptionRests 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.

Probably not a substantial claim: may not pass S3 (load-bearing).

All mouse experiments performed were approved by the Institutional Animal Care and Use Committee of Peking University.

“All of the mouse experiments performed were approved by the Institutional Animal Care and Use Committee of Peking University.”