Table 1.
Preclinical animal studies testing MSC transplantation to augment bone formation
| Author | Ref. | Animal model | Source/delivery/dose mouse (M) human (H) | Engraftment | Outcome |
|---|---|---|---|---|---|
| Ichioka (2002) | 66 | SAMP6 (age‐related osteoporosis) | WBM (M) /intrafemural/3 × 107 cells | Not quantified | Increase in trabecular bone. Normalization of BMD and BM environment |
| Hsiao (2010) | 67 | OVX mice (Postmenopausal osteoporosis) | Transgenic MSCs (M) (GFP)/IV/ 1.5 × 106 GFP‐MSCs on day 0, 6, 12, 18, 24, and 30 | Not quantified, GFP signal present in trabecular and cortical bone (2 months) | Improvement in endochondral BMD and slight improvement in BV/TV |
| Ma (2015) | 68 | MRL/lpr mice (Secondary osteoporosis) | Human BMSCs/IV/ 1 × 104 cells per g | Not quantified | Improvement of BMD and trabecular bone formation |
| Cho (2009) | 69 | OVX mice (Postmenopausal osteoporosis) | Transgenic MSCs (M) (CXCR4 and Rank‐Fc)/IV/2 doses (6–7 × 105 cells; day 0/7) | 2% (48 hours) | Prevention of BMD decline |
| Lien (2009) | 70 | Glucocorticoid‐induced secondary osteoporosis (C3H/HeN) | Transgenic MSC‐like cell line (M) (CXCR4 and CXCR4/Cbfa‐1)/IV/1 × 106 | 1.5% (7 Days) | Restoration of bone formation, stiffness and strength |
| Singh (2013) | 71 | Wrn‐/‐/Terc‐/‐ accelerated aging. (Age‐related osteoporosis) | WBM (M)/IV/5 × 106 | MSCs present in bone marrow. 6%‐20% of femoral osteocytes and 5%‐15% of femoral osteoblasts were donor derived (10.5 months) | Delay in microarchitectural deficiencies associated with Wrn/Terc mice |
| Kiernan (2016) | 72 | Sca‐1–/– mouse (Age‐related osteoporosis) | WT/Transgenic (GFP) MSCs (M)/IV/2 × 106 | Bone marrow (0.1 to 4.5 cells/million), lungs (2,300 cells/million) documented by flow cytometry and qPCR (6 months) | Improvement in bone formation and overall turnover. Improved microarchitecture |
| Sackstein (2008) | 73 | NOD/SCID mice | MSCs (H) (Modified CD44)/IV/5 × 106 | Not quantified, present on endosteal surface (12 weeks) | Small amount of human osteoid documented |
| Guan (2012) | 74 | OVX (Postmenopausal) and aged C57BL/6 mice (Age‐related osteoporosis) | Transgenic MSCs (H) (GFP w/ LLP2A ligand/IV/dose not specified | Not quantified, large numbers of transplanted cells present on trabecular surface | Complete resolution of osteoporosis. Increase in bone formation |
| Liu (2015) | 75 | MRL/lpr mice (Secondary osteoporosis) | WT (M) MSCs/IV/ 0.1X106 cells per 10 g body weight | Not quantified | Amelioration of osteopenia, restoration of native BMSC function in MLR/lpr mice |
| Sui (2016) | 76 | Glucocorticoid‐induced secondary osteoporosis (C57BL/6) | MSCs (M) from untreated C57BL/6 mice/IV/1 × 106 | Not quantified, but present for at least 4 weeks | MSC transplant prevented the loss of bone volume and strength. |
Table 1 documents specific reference, animal model, donor engraftment, MSC source/delivery/dose, and outcome for all preclinical studies using MSC transplant to increase bone formation in various rodent models of osteopenia. Abbreviations: BMSCs, bone marrow stromal cells; BMD, bone mineral density; BVTV, Bone volume fraction; GFP, green fluorescent protein; MSC, mesenchymal stromal cells; OVX, ovariectomized; WBM, whole bone marrow; WT, wild type.