Gene

Genetic enhancement

Cell biology

Oncolytic virus

Haematopoiesis

Induced pluripotent stem cell

Biology

Mesenchymal stem cell

Transplantation

Stem cell

Cancer research

Biochemistry

Computational biology

Drug discovery

Bioinformatics

Embryonic stem cell

Stem-cell therapy

Tumor cells

Internal medicine

Medicine

Nature Reviews Drug Discovery

Naturally occurring stem cells isolated from humans have been used therapeutically for decades. This has primarily involved the transplantation of primary cells such as haematopoietic and mesenchymal stem cells and, more recently, derivatives of pluripotent stem cells. However, the advent of cell-engineering approaches is ushering in a new generation of stem cell-based therapies, greatly expanding their therapeutic utility. These next-generation stem cells are being used as ‘Trojan horses’ to improve the delivery of drugs and oncolytic viruses to intractable tumours and are also being engineered with angiogenic, neurotrophic and anti-inflammatory molecules to accelerate the repair of injured or diseased tissues. Moreover, gene therapy and gene editing technologies are being used to create stem cell derivatives with improved functionality, specificity and responsiveness compared with their natural counterparts. Here, we review these engineering approaches and areas in which they will help broaden the utility and clinical applicability of stem cells. Primary stem cells have long been used therapeutically for applications such as bone marrow transplantation. This Review discusses how cell-engineering approaches are enabling the development of next-generation stem cell therapies with improved function, specificity and responsiveness, thereby expanding their applications into areas such as delivering drugs and oncolytic viruses to tumours and promoting tissue repair in various diseases.

Next-generation stem cells — ushering in a new era of cell-based therapies