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Updated: Aug 18, 2026

Megakaryocyte Differentiation and Platelet Formation from Human Cord Blood-derived CD34+ Cells
Published on: December 27, 2017
In vivo platelet production from mature megakaryocytes: does platelet release occur via proplatelets?
1Surgery II, Osaka University Medical School, Japan.
Abstract:
Although platelets are universally accepted to be born from megakaryocytes (MKs), the mechanism by which platelets are formed and released from MKs in vivo remains controversial. One theory, known as the proplatelet theory, postulates that platelets are released from proplatelet processes protruding from MKs into sinusoids located in the bone marrow hematopoietic compartment. Proplatelet formation (PPF) has been observed in in vitro experiments involving detailed analyses of related molecular events. PPF has also been used as a marker of MK maturation. However, PPF is suggested to be a nonphysiological phenomenon. On the other hand, transmission electron microscopy (TEM) analyses have revealed platelet formation via explosive fragmentation of MK cytoplasm in bone marrow and lung capillaries prepared by immersion fixation. Moreover, TEM and scanning electron microscopy studies of liquid-cultured MKs kept in suspension show that platelet formation occurs without PPF. Rather, an explosive and global fragmentation of the MK cytoplasm composed of platelet territories has been reported as the mechanism of platelet formation. In addition, in vivo and ex vivo observations of platelet release from MKs with phase-contrast microscopy strongly support the explosive-fragmentation theory. With all observations taken into account, PPF may not be a prerequisite for platelet release from MKs under real-life conditions. In this review, a new "protoplatelet" concept is proposed to support the explosive-fragmentation theory. Additionally, the role of the lungs in platelet production is reviewed and discussed.
Insights
Platelet formation from megakaryocytes (MKs) may occur via explosive fragmentation, not solely through proplatelet processes. This review proposes a "protoplatelet" concept and discusses the lungs' role in platelet production.
Area of Science:
- Hematology
- Cell Biology
- Biophysics
Background:
- Platelet production is essential for hemostasis.
- The precise in vivo mechanism of platelet release from megakaryocytes (MKs) is debated.
- The proplatelet formation (PPF) theory is widely accepted but questioned.
Purpose of the Study:
- To review and critically evaluate current theories of platelet formation.
- To present evidence supporting explosive MK cytoplasm fragmentation.
- To introduce a novel "protoplatelet" concept and discuss the lung's role in platelet production.
Main Methods:
- Review of existing literature, including in vitro and in vivo studies.
- Analysis of transmission electron microscopy (TEM) and scanning electron microscopy (SEM) data.
- Phase-contrast microscopy observations of MKs.
Main Results:
- Evidence suggests platelet formation occurs via explosive fragmentation of MK cytoplasm, not exclusively through PPF.
- PPF may not be a prerequisite for physiological platelet release.
- The lungs may play a significant role in platelet production.
Conclusions:
- Explosive fragmentation is a plausible mechanism for platelet formation.
- "Protoplatelet" concept offers an alternative framework.
- Further research is needed to elucidate the complete process and the lung's contribution.
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