Thrombopoietin (TPO) is an hepatocyte-derived growth factor reported to augment stem cell factor (SCF)-induced human mast cell (HuMC) growth. We therefore explored the ability of TPO alone to support HuMCs.

Human CD34+ pluripotent and CD34+/CD117+/CD13+ HuMC progenitor cells were cultured in serum free media (SFM) with rhTPO under conditions developed for culturing megakaryocytes (MKs), and the outgrowth of HuMCs quantitated. We also examined the effect of rhTPO on CD34+ and CD34+/CD117+/CD13+ cells cultured with rhSCF, rhIL-3 and/or rhIL-6 on HuMC development. TPO levels were further assessed in patients with mastocytosis.

With rhTPO alone, human CD34+ cells at 2 wks differentiated into CD61+/CD41+/CD42a+/CD42b+/CXCR4+ MKs (85-90%) and FcϵRI+/CD117+/CD13+ HuMCs (5-10%). CD34+/CD117+/CD13+ derived SCF-independent HuMCs also expressed CD41+, TPO (c-Mpl) receptors, tryptase and chymase, and were capable of surviving in SFM with rhTPO alone for two wks or longer, when recultured in rhSCF and rhIL-6. HuMC numbers were augmented when 10 ng/ml rhTPO was combined with 10 ng/ml rhSCF. The addition, however, of 50 ng/ml rhTPO did not augment, and in fact, inhibited HuMC growth when rhSCF was combined with rhIL-3 and/or rhIL-6. In patients with mastocytosis, TPO levels did not correlate with disease severity or platelet counts.

RhTPO, acting presumably through its receptor c-Mpl, will support HuMCs. The effect of TPO on HuMC growth from progenitors in the presence of rhSCF alone, or in combination with rhIL-3 and/or rhIL-6 varies, depending on the relative amount of each growth factor. We found no evidence of a role for TPO in mastocytosis.