Preclinical modeling of hematopoietic stem cell transplantation – advantages and limitations

Abstract

Hematopoietic stem cell transplantation, which was first successfully performed in the 1950s, remains a critical therapeutic modality for treatment of a diverse array of diseases, including a multitude of hematological malignancies, autoimmune disorders, amyloidosis and inherited genetic hematological disorders. Although great advances have been made in understanding and application of this therapy, significant complications still exist, warranting further investigation. Of critical importance, graft‐versus‐host disease (GVHD), in both acute and chronic forms, remains a major complication of hematopoietic stem cell transplantation, responsible for both the development of chronic illness and morbidity, as well as mortality. Use of an appropriate preclinical model may provide significant insight into the mechanistic pathways leading to the development and progression of graft‐versus‐host disease, as well as cancer in general. However, existing preclinical modeling systems exhibit significant limitations, and development of models that recapitulate the complex and comprehensive clinical scenario and provide a tool by which therapeutic intervention may be developed and assessed is of utmost importance. Here, we review the present status of the field of graft‐versus‐host disease research. We discuss and summarize the preclinical models currently in use, as well as their advantages and limitations.

Bone marrow stem cell applied in the canine veterinary clinics

“…Additionally, several studies demonstrated, the regenerative function of these cells in damaged tissues (Narazaki & Cristante 2011, Ryu et al 2012, Bittencourt et al 2016, Stolfi et al 2016.…”

“…(Friedenstein et al 1974, Tharasanit et al 2011, Rici et al 2012, Kim et al 2013, Hu et al 2014 postnatal life, is the most studied, having two lines of stem cells: hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) (Bittencourt et al 2006, BydlowskI et al 2009, Narazaki & Cristante 2011 (Fig.1 and 2). Furthermore, BMSC is the main source of stem cells, because of its easy isolation, and more than one to six millions of mesenchymal or/and hematopoietic stem cell can be isolated, cultured and applied without problem from one isolation (Oliveira et al 2010, Ryu et al 2012, Bittencourt et al 2016, Stolfi et al 2016.…”

“…On the other hand, mesenchymal stem cell from BMSC can be used in the veterinary clinic for example, in the treatment of bone fractures, spinal cord damage and dermatitis (Pereira et al 2008, Bydlowski et al 2009, Ryu et al 2012, Bittencourt et al 2016, Stolfi et al 2016). Thus, this study aimed to carry out a short-review about bone marrow stem cell and check their applicability in the treatment of various diseases in the canine.…”

“…The aspiration usually occurs in the epiphysis of long bones, such as the greater trochanter of the femur and greater tuberosity of the humeral bone, iliac crest and trans-iliac area in vivo. In dogs, the region of the iliac crest is widely used due to its location within easy reach (Raskin 1998, Ryu et al 2012, Bittencourt et al 2016, Stolfi et al 2016.…”

“…In dogs, the presence of HSCs have been observed mostly in bone marrow and umbilical cord blood, being used in cell therapy for neoplasia, hematological, metabolic, and immunological diseases (Bruno et al 2009, Nakage et al 2009, Ryu et al 2012, Bittencourt et al 2016, Stolfi et al 2016.…”