ProTrans (pooled Wharton's jelly MSCs)

Overview

ProTrans is an off-the-shelf allogeneic cell therapy developed by Swedish biotech NextCell Pharma in collaboration with Professor Per-Ola Carlsson at Uppsala University. Rather than harvesting bone marrow or adipose tissue from individual patients, ProTrans isolates mesenchymal stromal cells (MSCs) from Wharton's jelly of donated human umbilical cords and pools cells from five independent donors using NextCell's proprietary selection algorithm (Auto-select) designed to maximize immunomodulatory potency and batch-to-batch consistency.

Because Wharton's jelly MSCs express low levels of HLA class I and virtually no HLA class II or costimulatory molecules, ProTrans is administered as a single fixed-dose peripheral intravenous infusion (200 million cells) without HLA matching, lymphodepletion, or chronic anti-rejection drugs. In the body, the infused stromal cells act through paracrine signaling — secreting anti-inflammatory cytokines, indoleamine 2,3-dioxygenase (IDO), prostaglandin E2, and trophic factors that dampen autoreactive T-cell activation, promote endogenous regulatory T cells (Tregs), and reduce inflammatory stress inside pancreatic islets.

Key Clinical Evidence

Adult Phase 1/2 Trial (ProTrans-1 & ProTrans-2, NCT03406585)

The foundational NCT03406585 study enrolled 24 adults aged 18–40 diagnosed with Stage 3 Type 1 Diabetes within the preceding 24 months who retained fasting plasma C-peptide above 0.12 nmol/L (0.36 ng/mL) and maintained target fasting blood glucose near 70–180 mg/dL (3.9–10.0 mmol/L). Results were published in Diabetologia by Carlsson et al. in August 2023 (PMID: 37221247):

• Part 1 (ProTrans-1, open-label dose escalation, n = 9): Three cohorts of three patients each received a single intravenous infusion of 25 million (low), 100 million (medium), or 200 million (high) ProTrans cells. C-peptide preservation at 12 months was dose-dependent, with the 100 million and 200 million cohorts preserving endogenous insulin secretion significantly better than the 25 million cohort, establishing 200 million cells as the fixed clinical dose.
• Part 2 (ProTrans-2, randomized 2:1, double-blind, placebo-controlled, n = 15): Ten adults received a single intravenous infusion of 200 million ProTrans cells and five received matched placebo:
  • Primary Endpoint (12-Month MMTT C-Peptide AUC): Stimulated C-peptide declined by only 10% over 12 months in the ProTrans arm compared with a 47% loss in the placebo arm (p < 0.05).
  • Exogenous Insulin Requirements: Median daily insulin requirements increased by +10 U/day over 12 months in placebo recipients versus 0 U/day (no median increase) in ProTrans recipients (p < 0.05).
  • Safety & Immunogenicity: No serious treatment-related adverse events, infusion reactions, or donor-specific HLA antibodies were observed.

Long-Term Follow-Up & Repeat Dosing (ProTrans-Obs & ProTrans-Repeat, NCT03973827)

• 5-Year Single-Dose Follow-Up (ProTrans-Obs): Participants from the randomized ProTrans-2 cohort were tracked for five years without additional treatment. NextCell reported that single-dose ProTrans recipients retained an average of 57% of baseline endogenous insulin secretion at Year 5 compared with 15% in placebo recipients.
• Repeat-Dose Study (ProTrans-Repeat, NCT03973827, n = 15): All nine participants from the dose-escalation ProTrans-1 cohort received a second booster dose at their original dose level 12 to 18 months after the first infusion and were compared with six matched untreated control patients. In company-reported 6-year follow-up (~5 years after the second dose), the three patients in the high-dose (200 million cells × 2) cohort retained an average of 91% of baseline stimulated C-peptide (with two of the three showing higher C-peptide than at baseline), without treatment-related safety signals or allosensitization. Because the high-dose repeat subgroup comprises only three patients (n = 3) in an open-label extension, peer-reviewed publication and larger randomized confirmation remain necessary.

Pediatric & Adolescent Trial (ProTrans-Young, NCT05061030)

ProTrans-Young (NCT05061030) is an investigator-initiated Phase 1/2 trial led by Prof. Per-Ola Carlsson at Uppsala University Hospital enrolling 66 children and adolescents aged 7–21 with newly diagnosed T1D:

• Phase 1b (open-label safety, n = 12): Six adolescents (ages 12–18) and six children (ages 7–11) received ProTrans with clean safety review board clearance.
• Phase 2 (randomized 1:1, double-blind, placebo-controlled, n = 54): Thirty participants aged 12–21 and thirty participants aged 7–11 were randomized to ProTrans or placebo. In April 2025, NextCell reported interim 12-month data from the older 12–21 subgroup showing favorable safety and numerical trends toward C-peptide preservation, but noted that an unusually prolonged post-diagnosis "honeymoon" phase in both active and placebo arms masked statistically significant group separation at the 12-month timepoint. Dosing of the younger 7–11 cohort completed in mid-2025, with 1-year and 5-year follow-up continuing through September 2028.

Limitations & Watch Items

1. Sample Size of Randomized Evidence: While ProTrans-2 (NCT03406585) is a rigorous double-blind randomized controlled trial published in Diabetologia, the randomized Part 2 cohort included 15 patients (10 active, 5 placebo).
2. Pediatric ProTrans-Young 7–11 Readout & Longer Follow-Up: Because the interim 12-month analysis of the 12–21 cohort in NCT05061030 did not achieve statistical separation from placebo at Year 1, the full combined readout across both pediatric age strata (7–11 and 12–21) and 24-month post-honeymoon divergence will be critical to determine whether a single fixed MSC infusion reliably preserves beta-cell function in youth.
3. Peer-Reviewed Publication of Long-Term Extensions: Full peer-reviewed publication of the 5-year ProTrans-Obs and ProTrans-Repeat (NCT03973827) datasets is needed to verify individual patient trajectories and responder characteristics.

Summary of Strengths & Limitations

Strengths

• Fixed-dose, off-the-shelf allogeneic cell product pooled from five umbilical-cord donors — requires no HLA matching, no patient leukapheresis, and no conditioning chemotherapy
• Randomized, double-blind, placebo-controlled Phase 2 data (Carlsson et al., Diabetologia 2023) showed only a 10% decline in stimulated C-peptide at 12 months versus a 47% decline on placebo (p < 0.05), with stable exogenous insulin needs (0 U/day median change versus +10 U/day on placebo)
• Clean safety profile across adult Phase 1/2 (NCT03406585), repeat-dose (NCT03973827), and pediatric/adolescent (NCT05061030) cohorts, with zero serious treatment-related adverse events or host HLA allosensitization

Limitations

• {'The randomized Phase 2 adult efficacy cohort was small (n = 15': '10 active versus 5 placebo), and a definitive pivotal Phase 3 trial has not yet been completed'}
• Interim 12-month data from the older adolescent cohort (ages 12–21) of the pediatric ProTrans-Young trial (NCT05061030) did not show statistically significant separation from placebo at 1 year due to prolonged honeymoon C-peptide retention in both groups
• Long-term 5- to 6-year C-peptide preservation reports (ProTrans-Obs and ProTrans-Repeat) come from very small completer subgroups (n = 3 at the high repeat dose) in company announcements rather than large peer-reviewed cohorts