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Updated: May 3, 2026
Isolating Mesangiogenic Progenitor Cells MPCs from Human Bone Marrow
Published on: July 15, 2016
Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine
T D Bartley1, J Bogenberger, P Hunt
1Amgen, Incorporated, Amgen Center, Thousand Oaks, California 91320.
Abstract:
A novel megakaryocyte growth and development factor (MGDF) has been identified in aplastic canine plasma, and its cDNAs have been cloned from canine, murine, and human sources. Purified canine MGDF isolated by procedures involving MpI receptor affinity chromatography exists in at least two forms, with apparent molecular masses of 25 kDa and 31 kDa, that share the N-terminal amino acid sequence APP-ACDPRLLNKMLRDSHVLH. Human, dog, and mouse cDNAs for MGDF are highly conserved and encode open reading frames for proteins of 353, 352, and 356 amino acids, respectively, including predicted signal peptides. Canine MGDF and recombinant human MGDF support the development of megakaryocytes from human CD34+ progenitor cell populations in liquid culture and promote the survival of a factor-dependent murine cell line (32D) engineered to express MpI. These biological activities are blocked by the soluble extracellular domain of MpI. These data demonstrate that MGDF is a novel cytokine that regulates megakaryocyte development and is a ligand for the MPI receptor.
Insights
A novel megakaryocyte growth and development factor (MGDF) was discovered and cloned. This cytokine regulates megakaryocyte development and binds to the MPI receptor.
Area of Science:
- Hematology
- Molecular Biology
- Cell Biology
Background:
- Megakaryocyte development is crucial for platelet production.
- The specific factors regulating megakaryopoiesis are not fully elucidated.
- Aplastic canine plasma yielded a novel growth factor.
Purpose of the Study:
- To identify and characterize a novel megakaryocyte growth and development factor (MGDF).
- To determine the role of MGDF in megakaryocyte development and its receptor interaction.
- To investigate the conservation and function of MGDF across species.
Main Methods:
- Cloning of MGDF cDNAs from canine, murine, and human sources.
- Purification of canine MGDF using MpI receptor affinity chromatography.
- Assessing biological activities of MGDF on human progenitor cells and a murine cell line expressing MpI.
Main Results:
- Identified and cloned MGDF cDNAs from multiple species, showing high conservation.
- Purified canine MGDF exists in 25 kDa and 31 kDa forms with a shared N-terminal sequence.
- MGDF supports megakaryocyte development and cell survival, with activity blocked by soluble MpI.
Conclusions:
- MGDF is a novel cytokine regulating megakaryocyte development.
- MGDF functions as a ligand for the MPI receptor.
- MGDF plays a significant role in hematopoiesis and megakaryopoiesis.
