What is the effect of human placental extract with umbilical cord stem cells on Crohn's disease?

Effect of Human Placental Extract with Umbilical Cord Stem Cells on Crohn's Disease

Allogeneic stem cell therapy, including placental and umbilical cord-derived stem cells, shows promise for treating complex perianal fistulae in Crohn's disease but has limited evidence for treating intestinal Crohn's disease itself. 1

Efficacy for Perianal Fistulizing Crohn's Disease

• Allogeneic adipose-derived stem cells demonstrated significantly higher combined remission rates (56.3% vs 38.6%) compared to placebo in treating complex perianal fistulae in the pivotal ADMIRE CD trial 1
• A meta-analysis of 11 studies, including three RCTs, showed improved healing rates with allogeneic stem cell therapy compared to control treatments 1
• The safety profile appears favorable, with no significant difference in serious adverse events between stem cell therapy and placebo groups (24.3% vs 20.6%) 1

Umbilical Cord Mesenchymal Stem Cells for Intestinal Crohn's Disease

• A randomized controlled trial of umbilical cord mesenchymal stem cells (UC-MSCs) showed significant improvements in Crohn's disease activity index (CDAI) and Harvey-Bradshaw index (HBI) after 12 months compared to controls 2
• UC-MSCs allowed for significant reduction in corticosteroid dosage (4.2±0.84 mg/day vs 1.2±0.35 mg/day in controls) 2
• Only mild adverse events (fever in some patients) were reported with no serious adverse events 2

Placental-Derived Products for Crohn's Disease

• PDA-001 (cenplacel-L), a preparation of placenta-derived mesenchymal-like cells, demonstrated clinical response in 36% of subjects with moderate-to-severe Crohn's disease compared to 0% in the placebo group 3
• One treatment-related serious adverse event (systemic hypersensitivity reaction) occurred at the highest dose (8 units) 3
• Current guidelines do not specifically recommend placental extract with umbilical cord stem cells for intestinal Crohn's disease management 1

Mechanism and Delivery Methods

• Stem cells appear to work by modifying immune response and promoting healing processes in Crohn's disease 4
• Different delivery methods affect efficacy - higher healing rates were reported when stem cells were combined with fibrin glue (71%) or impregnated on a fistula plug (83%) versus direct injection (50%) 1
• The optimal mode of delivery, dose, and frequency of injections still need to be determined in further studies 1

Current Limitations and Considerations

• There are currently no long-term follow-up data available on safety and effectiveness 1
• No standardized guidelines exist regarding dose, number of administrations, route of administration, or specific type of stem cells to use 4
• Only one commercial mesenchymal stem cell preparation (Darvadstrocel/Cx601) is currently FDA-approved for refractory Crohn's-associated complex perianal fistula 4
• Patient selection criteria remain unclear, with most studies excluding patients with more than two internal and three external fistula openings, rectovaginal fistulae, and those with anal/rectal stenosis or proctitis 1

Recent Evidence on Overall Efficacy

• A 2024 umbrella review of systematic reviews found stem cell therapy showed a 29.9% increased likelihood of clinical remission compared to controls and a 35.8% increased likelihood of healing perianal Crohn's disease 5
• The safety profile was comparable to conventional therapies, with no significant difference in adverse events (RR: 0.972) or serious adverse events (RR: 1.136) 5

Practical Considerations

• Autologous stem cells require cell harvesting through additional procedures like liposuction, while allogeneic stem cells (including placental/umbilical cord-derived) don't require this step 1
• Resource use for these interventions is high as they require access to cell culture facilities and specialized processing 1
• The high cost may decrease equity and feasibility, particularly in healthcare systems in low-income countries 1

Human placental extract with umbilical cord stem cells shows promise for Crohn's disease treatment, particularly for complex perianal fistulae, but more research is needed before it can be widely recommended for intestinal Crohn's disease management.