Exploitation of stem cell homing for gene delivery

Abstract

Stem cells have been the focus of numerous investigations to treat diseases as far ranging as diabetes, chronic heart failure and multiple sclerosis over the past decade. The process of stem-cell-based repair of acute injury involves homing and engrafting of the stem cell of interest to the site of injury followed by either differentiation of the stem cell to indigenous end-organ cells or liberation of paracrine factors that lead to preservation and/or optimization of organ function. Recognition of the ability of stem cells to home to sites of acute injury suggests that, if appropriately defined and harnessed, stem cell homing could serve as a means of local drug delivery through the infusion of genetically engineering stem cells that secrete gene products of interest. The authors have recently demonstrated the use of this approach in preclinical studies of acute myocardial function. In addition, the use of engineered cells that home to appropriate niches have been used to correct genetic deficiency states (i.e., severe combined immunodeficiency, diabetes mellitus) in patients with otherwise chronic debilitating diseases. This review focuses on exploiting stem cell homing for gene transfer and on the state of the art and the challenges that face the field.

The Stem Cell Niche Should be a Key Issue for Cell Therapy in Regenerative Medicine

“…This cell therapy together with the trophic and immunomodulatory effects of MSCs, open an encouraging door for an allogeneic MSC therapy, even for genetic deficiencies, autoimmune diseases, etc. [17]. MSCs as "universal donors" for the treatment of autoimmune diseases may be a substantial clinical advantage.…”

New Era of Cell-Based Orthopedic Therapies

“…In this regard, it maybe that deficiencies in autologous MSCs may account for some autoimmune diseases or immunodestructive conditions. Several assays can now be envisioned to determine if certain clinical conditions arise 59 or are maintained because of defects in specific tissue MSCs=pericytes.…”

Mesenchymal Stem Cells in Regenerative Medicine

“…By occluding a major artery leading to the brain or nurturing the heart (Penn and Khalil, 2008), mouse models of stroke or AMI have been created. From 2 to 7 days after creating these models of severe ischemia, hMSCs are injected via the tail vein Penn and Khalil, 2008).…”

“…From 2 to 7 days after creating these models of severe ischemia, hMSCs are injected via the tail vein Penn and Khalil, 2008). The animals are monitored for 5e10 weeks, and those that receive hMSC therapy return to full and normal function.…”