Abstract: Cerebral stroke, particularly the ischemic type, is one of the leading causes of disability and mortality worldwide. Alarmingly, the incidence of ischemic stroke is rising, especially among younger populations (Zhang et al., 2025). This concerning trend highlights the urgent need to develop and improve therapeutic strategies for stroke prevention and management. Current disease-modifying treatments for ischemic stroke primarily focus on restoring blood flow by dissolving the obstructing clot using enzymes such as tissue plasminogen activator or through mechanical thrombectomy. However, these interventions are limited by a narrow therapeutic time window, rendering a large proportion of patients ineligible. As a result, many stroke survivors experience long-term neurological deficits. These patients could benefit from regenerative therapies aimed at restoring damaged neural tissue. Even partial recovery could improve the quality of life of the patient group, also reduce the burden on health system. In this context, we propose a comprehensive regenerative approach for stroke using a combination therapy that includes sequential transplantation of genetically engineered, multiple cell types, along with gene therapy to promote neural differentiation. We also addressed the potential causes of poor grafting efficiency of transplanted cells and discussed strategies to overcome these challenges. This therapeutic strategy can be evaluated using animal models of stroke. We believe that such an approach could provide a more effective regenerative treatment option for stroke patients.