Table 6.
In Vivo Application of MSC Aggregates
| MSC source | Methods of aggregation | Transplanted tissues | In vivo effects | Ref. |
|---|---|---|---|---|
| Bone and cartilage regeneration | ||||
| Rabbit bone marrow | Fragment of 3D cell sheet | Subcutaneous site; Mandibule (fractured) | Twofold increase in bone formation compared to single-cell injection; | 141 |
| Rabbit bone marrow | 3D cell sheet | Subcutaneous dorsal pocket | New bone formation; enhanced compressive strength | 142 |
| Human bone marrow | Pellet culture | Skin | 24% increase in bone and 74% in marrow formation compared to controls | 143 |
| Human and rabbit synovium | Hanging drop | Left knee joint | Successful cartilage regeneration, the defect was fully filled with cartilage matrix | 22 |
| Rabbit articular cartilage and synovium | Low attachment dish with rotary shaker | Osteochondral defects in the legs | Effective restoration of articular cartilage; in vivo ECM production | 147 |
| Wound healing and neoangiogenesis | ||||
| Human gengiva | Low attachment dish | Tongue (oral mucositis) | Increased regeneration of damaged crypts, basal and epithelia layer, increased proliferation of mucosal epithelial cells compared to single cells | 12 |
| Human adipose tissue | Spinner flask | Ischemic limbs | Three to fivefold increase in local HGF, VEGF, and FGF-2; two to fivefold host cells expressing α-actin, ICAM-1, VCAM-1, and PECAM-1 compared to dissociated cells | 38 |
| Human umbilical cord | Hanging drop | Ischemic limbs | Increased number of microvessels and smooth muscle α-actin compared to dissociated cells | 148 |
| Human adipose tissue | Hanging drop | Diabetic wounds | A significant increase in the rate of wound closure compared to single cells due to ECM proteins and secreted soluble factors (e.g., HGF, MMP-2) | 79 |
| Cardiac tissue repair | ||||
| Human umbilical cord | Low attachment plate | Myocardium (infarcted) | Fourfold decrease in LV end-diastolic and systolic diameters, or LV fractional shortening compared to single cells | 59 |
| Rat bone marrows | Thermal responsive hydrogel | Intramyocardial injection | 23% greater LV fractional shortening when compared with the dissociated MSCs | 48 |
| Mice bone marrow | Thermal responsive hydrogel | Skeletal muscle | Cells entrapped into the muscular interstices; better retention of the transplanted cells | 33 |
| Human adipose tissue | Modified hanging drop | Intramyocardial injection | Improved cell retention, survival, and integration in a porcine model | 21 |
LV, left ventricular; ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion molecule 1; PECAM-1, platelet endothelial cell adhesion molecule 1; MMP-2, matrix metalloproteinase 2.