The invention relates to systems and therapeutic methods to reduce plaque causing Peyronie's disease. One approach uses high pressure injection of collagenase-containing composition into a penile plaque. Plaque disruption is enhanced by the mechanical force of the high pressure, followed by the enzymatic action of collagenase. Another approach uses collagenase as a pretreatment, followed by addition of adipose-derived stem cells ADSCs. The initial collagenase injection breaks down collagen (often more type III than type I in Peyronie's) to provide short term benefit. The longer-term benefit is provided by introduction of ADSCs to the plaque, which can produce cytokines and other signals for revascularization, and restoration of normal penile tissue. The resulting combination advantageously reduces the bulk of the plaque early on with ongoing reduction through the revascularization of the tissue. In addition, the treatment provides an advantageous shift of elastin and collagen ratios.