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Table 1 Summary of different protocols in vitro for the efficient yield of PLTs/MKs and their functionality

From: Platelet generation in vivo and in vitro

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)

  1. 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
  2. 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