The CD34+Thy1+ cell population: are they all stem cells?

Abstract

In a recent article in Experimental Hematology, Michallet et al. [1Michallet M. Philip T. Philip I. et al.Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma Impact of HSC dose on engraftment, safety, and immune reconstitution.Exp Hematol. 2000; 28: 858Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar] describe studies where multiple myeloma patients were transplanted with CD34+Thy1+ cells isolated from peripheral blood progenitor cell (PBPC) products. The authors reference previous studies and state “The Thy1+ subpopulation of CD34+ cells have self-renewal characteristics of human stem cells and are able to generate all hematopoietic lineages.” Based on these previous reports, the authors classify CD34+Thy1+ cells as human stem cells (HSC). They further conclude that CD34+Thy1+ HSC are capable of producing fast and durable hematopoietic engraftment at cell doses greater than 0.8 × 106 CD34+Thy1+ HSC/kg. Of the 25 patients enrolled in this study, only nine patients received greater than 0.8 × 106 CD34+Thy1+ HSC/kg, and a number of these patients had significant delays in the time to 50,000 platelets/uL (Table 1, taken from Tables 1 and 3 [1Michallet M. Philip T. Philip I. et al.Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma Impact of HSC dose on engraftment, safety, and immune reconstitution.Exp Hematol. 2000; 28: 858Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar]).Table 1Patients receiving >0.8 × 106 CD34+Thy+ HSC/kgPatient #Dose of CD34+Thy1+ cells (×106/kg)Day platelet >50,000/uL41.062972.691380.925191.8112102.939231.3811241.3823301.1072311.9913 Open table in a new tab These data suggest that only patients who received greater than 1.38 × 106 CD34+Thy1+ HSC/kg had rapid platelet engraftment, and, in fact, Patients 8 and 30 who received 0.92 and 1.10 × 106 CD34+Thy1+ HSC/kg, respectively, had very significant delays in platelet recovery (days 51 and 72, respectively). This reader was confused by the data presented in Table 1 which showed that the median percentage of Thy1+ cells in the CD34+ population was 48.7%. In other words, nearly half of the CD34+ cells are Thy1+, and by the definitions used in this report, are therefore HSC. This number is much higher than would be expected for HSC content. Other reports [2Briddell R. Stoney G. Schuster L. et al.Primitive hematopoietic progenitor cells in peripheral blood harvests of patients mobilized with rhSCF plus rhG-CSF.Exp Hematol. 1995; 23: 751aGoogle Scholar] have presented analysis of primitive phenotypes such as CD34+CD38− and CD34+HLADR− populations that represent less than 10% of the CD34+ population. In summary, analysis of the data presented in this manuscript suggests that the CD34+Thy1+ population represents an enriched stem cell population, but not all CD34+Thy1+ cells can be true stem cells. In addition, the numbers of CD34+Thy1+ cells required for rapid engraftment are almost comparable to the levels of CD34+ cells required for rapid engraftment (>2 × 106 CD34+/kg).