Adipose mesenchymal stromal cell therapy in a desperate case of right-hand ischemia

Abstract

Upper limb critical ischemia is rarely due to arteriosclerosis alone. Cases with no surgical option are even less frequent [1]. A growing body of evidence suggests possible benefits of regenerative medicine in this condition using stem cells and growth factors, especially in cases with no other options [2,3]. The use of adipose tissue–derived progenitors as a therapeutic has grown substantially in the past decade. Multiple laboratories have established that stromal cells similar to those identified in bone marrow can be isolated in a reproducible manner from adipose tissue that is either resected as intact tissue or aspirated using tumescent liposuction.The minced adipose tissue is then digested by one or more of the following: collagenase, dispase, trypsin or related enzymes. After neutralization of the enzymes, the released elements, defined as the stromal vascular fraction (SVF), are separated from the mature adipocytes by differential centrifugation.The SVF consists of a heterogeneous mesenchymal population of cells that includes not only adipose stromal and hematopoietic stem and progenitor cells but also endothelial cells, erythrocytes, fibroblasts, lymphocytes, monocyte/ macrophages and pericytes, among others.When SVF cells are seeded into culture, a subset of elongated cells begins to adhere to the tissue culture plastic ware (Figure 1A).These cells can be purified further using a combination of washing steps and culture expansion with media similar to those used for bone marrow mesenchymal stromal cells to deplete most of the hematopoietic cell population from the SVF cells. This process allows the emergence of an adherent cell population termed adipose tissue–derived stromal cells (ASC). Although ASC are less heterogeneous than SVF cells, they are by no means homogeneous. ASC include multipotent cells with the ability to differentiate into adipocytes, chondrocytes and osteoblasts, among other lineage pathways [4]. One main difference between SVF cell and ASC suspensions is the high level of CD45+ cells in the SVF cells and the low or undetectable level in ASC. The International Society for Cellular Therapy has proposed adaptation of the characterization strategy for MSC for the phenotyping of the SVF cells using multicolor analysis [4]. We report the case of a multifactorial dominanthand ischemia in which all surgical and endovascular options had been performed with no result before successful treatment with this new line of treatment, avoiding major amputation.