Table 1.
Summary of different protocols in vitro for the efficient yield of PLTs/MKs and their functionality
| Source of cells | Efficient yield of MKs | Efficient yield of PLTs | Platelet functionality | References |
|---|---|---|---|---|
| imMKCLs | No data | Three CD42b+ PLTs per Cl-2 imMKCL-MK; Ten PLTs per Cl-7 imMKCL-MK. |
CD42b+; CD61+; PAR1+; CD49b+; CD29+
Positive integrin αIIβ3 activation and platelet aggregation. However, imMKCLs platelets gave less robust responses than fresh human platelets Thrombogenic activity in mouse models of thrombocytopenia |
Nakamura et al. (2014) |
| iPSCs | No data | Average 9.8 × 105 platelets were generated from 3 × 104 ciPSCs. | The platelets were activated with ADP or thrombin and bound to fibrinogen The platelets had the same ultrastructures, OCS, and α-granules as peripheral platelets |
Nishimura et al. (2013) |
| A total of 2.06 × 109 MKPs were generated from 1.26 × 108 iPSCs, an average of > 16 MKPs per single iPSC input. | Approximately six platelets per MKP | iPSC platelets generated under completely serum- and feeder-free conditions are functional, forming platelet thrombi in vivo in macrophage-depleted NOD/SCID mice iPSC platelets circulated for at least 8 h in macrophage-depleted NOD/SCID mice |
Feng et al. (2014) | |
| ADSCs | Approximately 2 × 106 MKs were gained from 107 adipocyte precursor cells | 15 × 104 PLTs/107 adipocyte precursor cells | adipocyte precursor cell-derived platelets are in response to thrombin CD41+; CD42a+; CD42b+ P-selection surface expression (+) |
Matsubara et al. (2009) |
| 5 × 104 MKs from 106 3T3-L1 cells | 1 × 105 PLTs from 106 3T3-L1 cells | CD41+; CD42b+
The binding of fibrinogen to 3T3-L1-derived platelets was increased with stimulation by agonists |
Matsubara et al. (2010) | |
| (3.3 ± 1.8) × 104 MKs from 106 p45NF-E2-OP9 cells | (2.9 ± 2.6) × 105 PLTs from 106 p45NF-E2-OP9 cells | fibrinogen binding(+) and P-selection surface exposure(+) CD41+; CD42b+ |
Matsubara et al. (2013) | |
| hESSCs | 5.5 × 104 ± 500 MKs from 1.8 × 105 ± 642 hESSCs | 3 × 105 ± 360 PLTs from 1.8 × 105 ± 642 hESSCs | PLTs bind to fibrinogen and express CD62P after thrombin stimulation PLTs intracellular structures are similar to PLTs harvested from human peripheral blood |
Wang et al. (2012) |
Obviously it could be concluded from the table above that most of the culture systems that have been studied thus far are too inefficient to generate MKs/PLTs on a large scale. However, the advantage of using ADSCs for platelet production is obvious, since subcutaneous adipose tissues are easily obtained and available in quantity
imMKCLs immortalized megakaryocyte progenitor cell lines, Cl-2 clone 2, Cl-7 clone 7, PAR1 protease-activated receptor 1, ciPSCs canine induced pluripotent stem cells, OCS open canalicular system, MKP megakaryocyte progenitor, hESSCs human endometrial stromal stem cells