Author(s): Luis Rodriguez-Menocal 1,2, Marcela Salgado 1,2, Stephen Davis 1, Jill Waibel 1, Arsalan Shabbir 1, Audrey Cox 1, Evangelos V. Badiavas 1,2,*
Stem cell based therapies have the potential to address many disorders that currently have few if any therapeutic alternatives -. There are nevertheless special considerations that must be taken into account when considering cell-based therapeutics. Cells have several distinct properties that differ significantly from traditional agents such as their relatively large size and their rather fragile nature. The most common means of delivering cells systemically has been by intravenous infusion for purposes such as blood cell transfusion. For stem cell based therapies directed at specific tissue repair, a more localized delivery of cells might be preferred but how these locally administered stem cells will behave and where they will engraft is in many cases uncertain. Injection and surgical implantation techniques have been used when trying to administer cells locally to specific sites. With injections, the pressure gradient created during injection can cause significant damage to cells. The needle diameter chosen for injection also has to be carefully considered so cells are not damaged shearing forces. Alternatively, cells may also be delivered surgically by placement into the surgical field either alone or by incorporating them into a matrix material. Surgical techniques will however require compatibility with the wound healing process and embedding cells into matrices may impact their mobilization to targeted tissues. Developing unique methods of cell delivery will broaden the way in which cells can be used therapeutically. Delivering cells directly to broad areas at predetermined depths is also not possible with these techniques. We have examined the use of factional lasers to create micro-channels in the skin that may be used as conduits for cell delivery locally to tissues and also allow for systemic administration -. Fractional lasers can create microchannels and depending on the laser's parameters the size and depth of these channels can be controlled , . Nano and microparticles have been shown to be efficiently administered to depths down to 230 [mu]m by using fractional lasers and these particles have been shown to stay in the dermis for longer than 1 month . In this report we describe the delivery of lineage negative (Lin- ) bone marrow cells to the skin of irradiated mice using an ablative fractional laser with the goal of achieving functional bone marrow transplantation. Using fractional lasers, we have demonstrated that stem cells can be delivered to the skin, become systemically distributed, engraft into distant organs and remain functionally intact. The cells were given at predetermined depths and could cover broader areas in a more uniform fashion.
While this study may not suggest this model as an alternative for bone marrow transplantation, it does provides proof of concept that cell delivery by fractional lasers is a viable option for the delivery of intact functional cells, even to distant sites.
Materials and Methods
All animals and procedure were approved by the Institutional Animal Care and Use Committee (IACUC)...