EDTA Treatment
Some tissues like epithelium require Ca²⁺ and Mg²⁺ ions for their integrity. Disaggregation of such tissues is readily achieved by a treatment with Ethylene-diamine tetra-acetic acid prepared in a balanced salt solution. This treatment is used for separation of cells from established cultures of epithelial tissues.

Enzymatic disaggregation generally gives higher cell yields than the mechanical method. But it is more selective since only certain cell types will survive dissociation. Therefore, in practice, the tissues are often reduced to small clusters of cells by an enzyme like collagenase and these dusters are used to initiate cell culture.