Table 1. Comparison of humanized BM niche models used for hematopoietic xenotransplantation.
Mouse strain | Culture conditions/matrix and/or scaffold | Source and # of transplanted MSCs | Implantation of MSC | Time of hematopoietic transplantation | Route of hematopoietic transplantation | Type/number of transplanted hematopoietic cells | Conditioning | Reference # |
---|---|---|---|---|---|---|---|---|
NSG | Expansion in 10% pHPL containing media, extracellular matrix (Millipore) | BM 2 x 106 |
Subcutaneous injection | 6 – 10 weeks post MSC transplantation | Intraossicle iv |
UCB-CD34: 1 x 104 AML: 1 cell – 1.4 x 106 PMF: 2 x 103 – 5 x 104 |
Sublethal irradiation | 25 |
NSG | Expansion in 10% pHPL-containing media, resuspended in extracellular matrix (Millipore), admixed with ECFC | BM 1.5 x 106 + 1.5 x 106 ECFC |
Subcutaneous injection | 8 weeks post MSC transplantation | Iv | UCB-MNC: 2 x 106 MOLM13: 2 x 106 |
Sublethal irradiation | 41 |
NSG | Expansion in 10% pHPL-containing media, gene knock-down in MSC prior to transplantation, resuspended in extracellular matrix (Millipore), admixed with ECFC | BM 1.5 x 106 + 1.5 x 106 ECFC |
Subcutaneous injection | 8 weeks post MSC transplantation | iv | MOLM13: 2 x 106 Nalm6: 2 x 106 |
Sublethal irradiation | 40 |
BRG | Expansion in 5% pHPL-containing media, seeded onto biphasic calcium phosphate (BCP) particles, incubated for an additional 7 days in vitro in osteogenic media | BM 2 x 105 MSCs |
Surgical implantation | 8 weeks post MSC transplantation | Intracardiac intraossicle |
UCB-CD34: 1 x 105 – 5 x 105 MM: 1 x 106 – 5 x 106 |
none | 31 |
BRG & NSG | Expansion in 5% pHPL-containing media, seeded onto biphasic calcium phosphate (BCP) particles, incubated for an additional 7 days in vitro in osteogenic media | BM 2 x 105 MSCs |
Surgical implantation | 8 weeks post MSC transplantation | Intraossicle | AML: 5 x 104 – 4 x 106 |
Sublethal irradiation | 27 |
NSG | Expansion in 5% pHPL-containing media, seeded onto biphasic calcium phosphate (BCP) particles, incubated for an additional 7 days in vitro in osteogenic media | BM 2 x 105 MSCs |
Surgical implantation | 8 weeks post MSC transplantation | Intraossicle | UCB-CD34 transduced with BCR-ABL or MLL-AF9 |
Sublethal irradiation | 42 |
NSG | Expansion in 10% FBS containing media, seeded onto medical-grade polycaprolactone (mPCL) scaffolds coated with calcium phosphate (CaP), 4 weeks static, 4 week bioreactor | BM 3 x 105 MSCs |
Surgical implantation | 10 weeks post MSC transplantation | Iv (retro-orbital) |
UCB-CD34: 1.3 x 106 | Sublethal irradiation | 32 |
NSG | Expansion in 10% FBS containing media, seeded onto medical-grade polycaprolactone (mPCL) scaffolds coated with calcium phosphate (CaP), 6–8 weeks differentiation in bioreactor, supplemented with rhBMP7 | BM 3 x 105 MSCs |
Surgical implantation | Up to 14 weeks post transplantation | Iv (retro-orbital) |
UCB/BM-CD34: 1 x 104 – 2 x 105 |
Sublethal irradiation | 33 |
SCID-beige | Expansion in 10% FBS-containing media, 21 days of chondrogenic differentiation in Pellet culture | BM 3 x 105 MSCs |
Surgical implantation | 3 weeks post transplantation | iv | UCB-CD34: 3 x 105 | Sublethal irradiation | 37 |
NSG | Expansion in 10% FBS-containing media, Seeding onto collagen sponges, culture for 2-7 days | BM 1 x 105 |
Surgical implantation | 48 hours before implantation | Intraossicle | UCB-CD34: 5 x 104 AML: 5 x 104 – 1 x 106 |
none | 28 |
BM: Bone Marrow, iv: intravenous; NSG: NOD-SCID IL-2Rγc-/-, BRG: BALB/c Rag2-/- IL-2Rγc-/-; MSC: Mesenchymal Stromal Cells, ECFC: Endothelial Colony Forming Cells, UCB: Umbilical Cord Blood, AML: Acute Myeloid Leukemia, PMF: Primary Myelofibrosis, pHPL: pooled Human Platelet Lysate; FBS: Fetal Bovine Serum