In a syngeneic transplantation model, 400 islet equivalents effectively reversed streptozotocin-induced diabetes, with therapeutic efficacy equivalent to Ficoll-purified islets (P > 0.05).<h4>Conclusions</h4>Our CD99-targeted immunomagnetic negative selection offers a novel, highly specific, and effective alternative for obtaining high-quality islets, as demonstrated by their excellent functional performance both in vitro and in vivo. The gene discussed is CD99; the disease is diabetes mellitus.