Intra-Articular Treatments

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Introduction

Perinatal-derived mesenchymal stem/stromal cells (MSCs) represent a next-generation biologic option for joint disease. Harvested from ethically donated umbilical cord and placental tissue, these cells are highly proliferative, immunomodulatory, and secrete potent trophic and anti-inflammatory factors. Unlike autologous sources, perinatal MSCs provide a consistent, high-yield cell population without requiring invasive harvesting procedures. Intra-articular delivery targets the site of pathology directly, with the aim of reducing inflammation, supporting cartilage matrix repair, and improving joint function.

Indications and Viable Conditions

Perinatal stem cell therapy may be considered in:

  • Mild-to-moderate osteoarthritis (Kellgren-Lawrence grade II–III).

  • Early cartilage degeneration and focal chondral defects in active patients.

  • Post-traumatic or post-meniscectomy joint degeneration.

  • Adjunctive therapy following joint-preserving surgery (microfracture, debridement, osteotomy).

  • Persistent inflammatory arthropathy refractory to conservative biologics.

Greatest benefit is observed when structural joint integrity is partially preserved; outcomes decline in end-stage “bone-on-bone” disease.

Patient Selection & Contraindications

Patient Selection

Ideal candidates include:

  • Age <70 with preserved joint space and imaging-confirmed early–mid stage degeneration.

  • Patients who have failed conservative care (NSAIDs, PT).

  • Non-smokers or individuals willing to optimize modifiable risks (weight reduction, glucose control).

  • Patients with realistic expectations, therapy is regenerative/biologic support, not a guaranteed cure.

Contraindications

Perinatal stem cell therapy should be avoided in:

  • Advanced osteoarthritis with complete cartilage loss.

  • Active joint or systemic infection.

  • Uncontrolled autoimmune/rheumatologic disease.

  • History of malignancy in the affected joint.

  • Current immunosuppressive therapy, coagulopathy, or cytotoxic drug exposure (consult over seeing provider of these conditions prior to any administration)

Dosing Considerations by Joint

While standardization is ongoing, relative intra-articular dosing of perinatal MSCs is typically adjusted by joint size:

  • Small joints (MTP, IP, small hand/wrist): ~5–10 million viable MSCs.

  • Medium joints (ankle, elbow, subtalar): ~20–30 million viable MSCs.

  • Large joints (knee, shoulder, hip): ~40–100 million viable MSCs.

Rationale: larger joints have greater synovial volume and cartilage surface area, requiring higher cell counts for effective coverage and paracrine signaling.

Important note: Intra-articular injections are technically demanding procedures. They should only be performed by practitioners who are properly trained and experienced with joint injections. Improper technique carries risks of neurovascular injury, tendon or ligament trauma, and direct articular cartilage damage. Ultrasound or fluoroscopic guidance is strongly recommended to ensure accurate placement and minimize risk.

Conclusion

Perinatal-derived MSCs provide a powerful, standardized, and ethically sourced cell population for intra-articular therapy. With proper patient selection and joint-specific dosing, these therapies may reduce pain, improve mobility, and potentially delay or avoid surgical intervention. Ongoing clinical trials continue to refine best practices, but current evidence supports their use in mild-to-moderate degenerative joint disease and focal cartilage pathology.

References

  1. Murphy MP, Wang H, Patel AN, Kambhampati S, Angle N, Chan K, et al. Allogeneic endometrial regenerative cells: An ‘off the shelf solution’ for critical limb ischemia? J Transl Med. 2008;6:45. doi:10.1186/1479-5876-6-45

  2. Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, et al. Mesenchymal stem cell therapy in the treatment of osteoarthritis: Reparative pathways, safety and efficacy – a review. BMC Musculoskelet Disord. 2016;17:230. doi:10.1186/s12891-016-1085-9

  3. Matas J, Orrego M, Amenabar D, Infante C, Tapia-Limonchi R, Cadiz MI, et al. Umbilical cord-derived mesenchymal stromal cells (MSCs) for knee osteoarthritis: A randomized double-blind placebo-controlled clinical trial. Stem Cells Transl Med. 2019;8(6):504–13. doi:10.1002/sctm.18-0121

  4. Pers YM, Rackwitz L, Ferreira R, Pullig O, Delfour C, Barry F, et al. Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: A phase I dose-escalation trial. Stem Cells Transl Med. 2016;5(7):847–56. doi:10.5966/sctm.2015-0245

  5. Gupta PK, Das AK, Chullikana A, Majumdar AS. Mesenchymal stem cells for cartilage repair in osteoarthritis. Stem Cell Res Ther. 2012;3(4):25. doi:10.1186/scrt116

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