Stem cell factor preparations

Thymic factors are naturally occurring substances that promote T-lymphocyte differentiation and differentiation of early stem cells into prothymocytes. Each of the available preparations (e.g., thymic humoral factor, thymosin fraction 5, and thymodulin) are mixtures of several polypeptides isolated from a calf thymus extract. 

X 10 against 2.4x 10 M s" for the preparations used in the pulse radiolysis experiments) so that the half-site reactivity has been seriously questioned by the presence of inactive enzyme in the earlier experiments Large differences in specific activity (up to a factor of two) and in the ability to protect mouse bone marrow stem cells against X-irradiation have been reported for five SOD preparations... 

It is probably unfair to expect that any single thymic polypeptide should have the capability of inducing the full maturation of precursor stem cells into mature functional T lymphocytes. It is perhaps more appropriate to hypothesize that the variety of well-defined thymic polypeptides act sequentially in the thymus to promote selected steps of T-cell differentiation similar to the sequential interactions seen in the complement and coagulation cas-case systems. Thus, the most informative studies concerning the mechanisms of thymic hormone actions are those that have employed prethymic precursor cells or thymocytes and specific assays to detect the influences of the preparation on various intracellular enzymes or cell surface markers that reflect the state of differentiation of the cell. A detailed schematic representation of the different steps in T cell differentiation (in man) was shown in Fig. 10 earlier in this chapter. Figure 10 has been generated from studies performed with both murine and human thymic precursor cells, and on the basis of such studies the hypothesized sites of actions of each of the well-characterized thymic factors are indicated. It would appear from the currently available information that some thymic factors (such as thymosin P3... 

The ability to prepare large quantities of pure recombinant MIP-la protein has been key for its preclinical in vivo evaluation (12,34). This section reviews studies used to confirm that recombinant MIP-la and BB-10010 retain the stem-cell-inhibitory properties identified in the natural factor by Lord et al. (2) and then describes new activities of MIP-la identified during preclinical evaluation, the mobilization of hematopoietic cells and the proliferation of primitive hematopoietic progenitors in ex vivo culture. 

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