Table 4.
Intramuscular‐MSC studies in healthy animals
| Disease model | Species model | I.S. | MSC source | Delivery site | Cell dose (×106) | Single/multiple | Engraftment & differentiation | Systemic effect | Bio‐distribution | Method of assessment of biodistribution/engraftment/differentiation | Study length | IM‐dwell time | Comments & general outcome | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Healthy | balbCnu/nu mice | N/A | HUCPVCs, hBMMSCs | Thigh skeletal muscle | 1 | Single, unilateral | Engraftment, did not assess differentiation | Not assessed | Transplanted site | Histology, bioluminescence | 5 m | 5 m | IM: 5 m dwell time and no distribution to organs | 5 |
| Healthy | NOD/SCID mice | N/A | bBMMSCs‐hBMMSCs‐hEPO | Quadriceps muscle | 1 | Single, bilateral | Engraftment, did not assess differentiation | Increased human EPO and hematocrit level | Not assessed | Secreted hEPO | 4 wk | 4 wk | Nonhuman primate MSCs can also be engineered to deliver biological products | 33 |
| Healthy | balbCnu/nu mice | N/A | hADMSCs | Thigh muscles | 1 | Single, bilateral | Engraftment, did not assess differentiation | Not assessed | Transplanted site and liver | Histology, bioluminescence imaging, genomic hybridization (hgDNA) | 8 m | 8 m | Majority of transplanted cells disappeared within 1 wk, 10% remained in the muscle through 8 m | 55 |
| Healthy | Nu/nu Foxn1 mice | N/A | hBMMSCs | Hind limb skeletal muscles | 1.5 | Single, bilateral | Engraftment, did not assess differentiation | Not assessed | Transplanted site | MRI | 26 days | 26 days | Significant reduction in signal between 3 to 12 days | 56 |
| Healthy | Merino‐cross sheep | N/A | sBMMSCs | Gastrocnemius muscle | 2 | Single, unilateral | Engraftment, did not assess differentiation | Not assessed | Transplanted site | Histology | 6 wk | 6 wk | CM‐DiI labeled sBMMSC into skeletal muscle showed dye retention for 6 wk | 47 |
| Healthy | NOD/SCID mice | N/A | PLX‐PAD | Thigh muscle | 1 | Single, 2 sites, unilateral | Engraftment, did not assess differentiation | Not assessed | Transplanted site | Histology, RT‐qPCR (hgDNA) | 3 m | 3 m | 80% of cells lost within 1 m. Neither single nor multiple caused toxicity | 57 |
Abbreviations: r, rat; m, mouse; h, human; p, porcine; s, sheep; b, baboon; d, day; wk, week; m, month; LIF, leukemia inhibitory factor; GM‐CSF, granulocyte‐macrophage colony‐stimulating factor; cTn1, cardiac troponin 1; HGF, hepatocyte growth factor; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; NGF, nerve growth factor; NT‐3, neurotrophin‐3; GFP, green fluorescent protein; gDNA, genomic DNA; cDNA, complementary DNA; RT‐qPCR, reverse transcription polymerase chain reaction; I.S., immunosuppressant.