Table 3.
Effects associated with MSC therapy in recent clinical SOT trials
| Observed Benefit | AE | No. Subjects (vs. control) |
Follow- up (months) |
Random | Setting | Type of MSC | MSC inoculum Time & Route |
Immunosuppression | Reference |
|---|---|---|---|---|---|---|---|---|---|
| Minimization of Immunosuppression Reduced rejection episodes Increased hematopoietic chimerism Donor-hyporesponsiveness in vitro | None | 100 vs. 100 | 18 | No | LDKT | Donor-specific, Allogeneic AT-MSC | Day -9, IP or IV | DST/HST/TBI aCD20/RATG/CyP CNI/AZA/Steroids | Vanikar 2011 |
| Induction of Treg Inhibition of memory T cells Donor-hyporesponsiveness in vitro | Elevated sCr | 2 | 12 | No | LDKT | Autologous BM-MSC | Day 7, IV | RATG/aCD25 CsA/MMF/Steroids | Perico 2011 |
| Alternative to anti-CD25 blockade Reduced maintenance CNI dose Early graft function Reduced acute rejection Reduced opportunistic infections | None | 102 vs. 51 | 12 | Yes | LDKT | Autologous BM-MSC | Day 0 and 14, IV | CNI/MMF/Steroids | Tan 2012 |
| Reduced maintenance CNI dose Transient increase of memory B cells | None | 6 vs. 6 | 12 | Yes | LDKT | Donor-specific, Allogeneic BM-MSC | Day 0 (IA) Day 30 (IV) | CyP CNI/Steroids | Pong 2012 |
| Minimization of Immunosuppression | None | 606 vs. 310 | 48 | No | LDKT | Donor-specific, Allogeneic AT-MSC | Day 3, IV | DST/HST/TBI RATG/CyP/IVIg CNI/MMF(AZA)/Steroids | Vanikar 2012 |
| Reduced tubulitis Reduced interstitial fibrosis/tubular atrophy Donor-hyporesponsiveness in vitro | Viral Infections | 6 | 5 | No | LDKT | Autologous BM-MSC | 6 months, IV | aCD25 CNI/MMF/Steroids | Reinders 2012 |
| Inhibition of memory T cells Donor-hyporesponsiveness in vitro | Acute Rejection | 2 | 12 | No | LDKT | Autologous BM-MSC | Day -1, IV | RATG CNI/MMF/Steroids | Perico 2013 |
| Increased Tregs Donor-hyporesponsiveness in vitro Increased IL10 levels | Acute Rejection | 7 | 12 | No | LDKT | Donor-specific, Allogeneic BM-MSC | Day 0, IO | RATG CNI/MMF/Steroids | Lee 2013 |
*Abbreviations:
aCD20: anti-CD20 antibody (Rituximab); aCD25: anti-CD25 andibody (Basiliximab); AT: Adipose Tissue; AZA: Azathioprine; BM: Bone Marrow; CNI: Calcineurin Inhibitor(s); CyP: Cyclophosphamide; DST: Donor specific leukocyte Transfusion; HSC: Hematopoietic Stem Cells; IA: Intra-Arterial; IO: Intra-Osseous; IP: Intraportal; IV: Intra-Venous; LDKT: Living Donor Kidney Transplant; MMF: Mycophenolate Mofetil; MSC: Mesenchymal Stromal (stem) Cell ; RATG: rabbit Anti-Thymoglobulin