Mesenchymal Stromal Cells Mediate Clinically Unpromising but Favourable Immune Responses in Kidney Transplant Patients

Table 3

Studies reporting the use of MSCs in kidney transplant patients (our study summary is at the end column).

Reference no.	Source	Dosage and route of administration	Patient number and groups	Immunosuppressive drugs	Follow-up period	Impact of MSC infusion
Perico et al. [24]	Autologous BM-MSCs	cells/kg MSCs were administered intravenously 7 days after KTx		Induction: basiliximab and low-dose ATG; Maintenance: CsA, MMF, and steroids	1 year	Increase in Tregs; Inhibition of the memory T cell; Reduction of CD8^+ T cell activity
Tan et al. [25]	Autologous BM-MSCs	of MSCs at kidney reperfusion and intravenously two weeks post-Tx	Group A = standard-dose CNIs+SCs; Group B = received low-dose CNIs+MSCs; Group C = control group received anti-IL-2R antibody+standard CNIs	TAC or CsA, MMF, and corticosteroids	1 year	Lower incidence of acute rejection; Decreased risk of opportunistic infection; Better estimated renal function at 1 year
Reinders et al. [26]	Autologous BM-MSCs	Two doses of 1– cells/kg of MSCs (7 days apart) 6 months after KTx were given to patients with subclinical rejection		Induction: basiliximab; Maintenance: CNI (TAC or CsA), MMF, and prednisone	24 weeks	Patients displayed a downregulation of the mononuclear cell proliferation assay; No change in T cells, B cells, NK cells, and monocytes
Perico et al. [27]	Autologous BM-MSCs	cells/kg MSCs infused intravenously one day pre-Tx		Induction: low-dose ATG; Maintenance: CsA, MMF, and steroids	1 year	Reduced memory CD8^+ T cells; Low donor-specific CD8^+ T cell cytolytic response; High Treg cells
Vanikar et al. [28]	Adipose-MSCs (AD-MSCs) and BM-HSCs	MSCs/kg+8- HSCs/kg 5 days before Tx through portal infusion	Group1 = AD-MSC+HSCs+drugs; Group 2 = HSC+drugs; Group 3 = drugs only	ATG, total lymphocyte irradiation, TAC, MEP	5-7 years	Better graft survival in groups 1 and 2
Pan et al. [29]	Donor-derived, BM-MSCs	MSCs were infused using a pressurizer during KTx; cells/kg were administered intravenously after 30 days of KTx	MSC group and non-MSC group	Induction: cytoxan and methylprednisolone; Maintenance: TAC, MMF, and prednisone	2 years	Low-dose TAC and MSCs were as effective as standard-dose TAC in graft survival after transplantation; No differences in CD19, CD3, CD34, CD38, and NK cells were detected
Perico et al. [30]	Autologous BM-MSCs	cells/kg MSCs were given intravenously at day 7 post-Tx () or at day 1 pre-Tx ()		Induction: basiliximab and low-dose ATG; Maintenance: low-dose CsA, MMF	5-7 years	Low circulating memory CD8^+ T cells (); Reduction of ex vivo donor-specific cytotoxicity (); Increase in the Treg cell/memory CD8^+ T cell ratio; High circulating levels of naïve and transitional B cells ()
Sun et al. [31]	Human umbilical cord-derived MSCs (UC-MSCs)	of MSCs via the peripheral vein before KTx; cells via the renal artery during KTx	MSC group and non-MSC group	Induction: ATG and methylprednisolone; Maintenance: CNI (TAC or CsA), MMF, and prednisone	1 year	UC-MSCs can be used as clinically feasible and safe induction therapy
Erpicum et al. [32]	Third-party bone marrow- derived MSCs (BM-MSCs)	of MSCs centrally infused on post-KTx	MSC group and non-MSC group	TAC, MMF, corticosteroids	1 year	Increased Treg frequencies; No significant change in B cell frequencies
Casiraghi et al. [7]	Autologous BM-MSCs	MSCs intravenously, one day before KTx	(case study)	Induction: low-dose ATG, D-0 to D-6 after KTx; Maintenance: CsA, MMF, methylprednisolone	9 years	Increased Tregs; Reduced memory CD8^+ T cells; Increased naïve B cells and transitional B cells; Safe withdrawal of maintenance drugs
Kaundal et al. [6]	Autologous BM-MSCs	Two doses of 1- MSCs intravenously, one day before and 30 days after KTx	Auto group and control group	TAC, MMF, methylprednisolone	2 years	Decrease in B cells; Increase in the transitional B cell subset
Dreyer et al. [33]	Third-party BM-MSCs	Two doses of allogeneic MSCs 6 months post-Tx		Induction: alemtuzumab; Maintenance: prednisone, low-dose TAC, and everolimus		No alterations in T and B cell populations or plasma cytokines; HLA-selected allogeneic MSCs combined with low-dose tacrolimus 6 months post-Tx are safe
Kaundal et al. (current manuscript)	Autologous BM-MSCs and allogeneic BM-MSCs	Two doses of 1- MSCs intravenously, one day before and 30 days after KTx	Auto group, allo group, and control group	TAC, MMF, methylprednisolone	2 years	Upregulation of naive T subsets and B regulatory and double-negative T cells; Clinical parameters normalized including Scr; Rejection episodes more in infused groups