Stem Cell Biology, Cell Therapy and Regenerative Medicine

Stem cells are the building blocks of the body. Stem cells are unique in that not only can they give rise to more stem cells but they also have the ability through a process called differentiation to become many different types of cells, such as skin cells, brain cells, lung cells and so on. 

Stem cells are a key component of regenerative medicine, as they open the door to new clinical applications. Some stem cells are multipotent in that they can become a variety of but limited number of different tissues, while other stem cells are pluripotent which means those cells can become every cell and tissue type in the body. Pluripotency is not always better than multipotency in that the former cannot be used directly in patients (but must first undergo differentiation in the laboratory) while the latter can often be used for treatment immediately upon isolation. Stem cells can be found throughout the body, being present in many tissues and organs (e.g., heart, brain and muscle), throughout one’s lifespan. Normally, these endogenous stem cells are responsible for the maintenance and repair of our organs and tissues. However, over time as we age our stem cells age and the stem cells can also be impaired by chronic disease and other changes in health status.

Regenerative medicine researchers are studying a variety of stem cell types, including multipotent adult stem cells (e.g., mesenchymal stem cells [MSC] found in adipose tissue and hematopoietic stem cells found in umbilical cord blood), as well as pluripotent stem cells such as the bioengineered cells called induced pluripotent stem cells (iPSC). Each cell type has unique qualities, with some being more versatile than others. Many of the regenerative therapies under development begin with the patient's own cells (called autologous therapies). For example, a patient's own skin cells may be collected, reprogrammed into iPSC in a laboratory to give them certain characteristics, and delivered back to the patient to treat his or her disease. Alternatively, a patient’s MSC may be harvested from their adipose tissue or bone marrow and immediately infused back into the patient.

Regenerative Medicine

Stem Cell Photos courtesy of Dr. Lalitha MadhavanRegenerative medicine is a revolutionary area of medicine with the potential to fully heal damaged tissues and organs, offering solutions and hope for people who have conditions that today are beyond repair. Regenerative medicine is a branch of biomedical translational research which deals with the “process of replacing, engineering, regenerating or repairing human cells, tissues or organs to restore or establish normal function.”  Regenerative medicine offers the promise of engineering damaged tissues and organs via stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs. Regenerative medicine refers to a group of biomedical approaches to clinical therapies that may involve the use of stem cells or progenitor cells.  Examples include the injection of stem cells or progenitor cells (cell therapies); the induction of regeneration by biologically active molecules administered alone or as a secretion from infused cells (immunomodulation therapy); and transplantation of in vitro grown organs and tissues (tissue engineering).  If a regenerated organ, tissue or cells could be derived from the patient’s own tissue or cells, this approach could potentially solve the problem of the shortage of organs available for donation, and the problem of organ transplant rejection. Regenerative medicine holds the promise of definitive, affordable health care solutions that heal the body from within. 

Three major approaches involved in the research related to regenerative medicine and cell therapy are:

  1. Rejuvenation (boosting the body's natural ability to heal itself), 
  2. Replacement (using healthy cells, tissues or organs from a living or deceased donor to replace damaged ones), and 
  3. Regeneration (delivering specific types of stem/progenitor cells or cell products to diseased tissues or organs to restore tissue and organ function). 

Nearly 128 million people (1 in 3 individuals in the United States) may benefit over their lifetime from regenerative medicine, including therapies for cardiovascular, neurological, and orthopedic diseases. Diseases such as myocardial infarction, stroke, and spinal cord injury might possibly be treated with greater efficacy using cell therapy based approaches rather than current treatment options. Translation of these potential therapies from the laboratory to the clinic requires that the stem cells are medically and economically available (via biobanking).  Political and ethical controversy surrounds the use of embryonic stem cells, and significant biological and regulatory concerns limit the clinical use of induced pluripotent stem cells (iPSC). Clinical trials using adult stem cells however, pose no such issues.  For example, cord blood stem cells have been used to treat cerebral palsy and peripheral vascular disease among others for several years via regenerative medicine.

Drs. Zain Khalpey, Klearchos Papas, Lalitha Madhavan and David Harris are investigating the therapeutic potential of using adult stem cells (e.g., mesenchymal stem cells and endothelial progenitor cells), iPSC and islet transplantation to treat ischemic heart failure, right heart failure associated with pulmonary hypertension, Alzheimer’s disease and Parkinson’s disease, and cerebral palsy. There are currently several exciting projects in which the investigators and clinician-scientists in the Division use adult progenitor cells to treat cardiovascular and neurological diseases and diabetes. In addition, Dr. Yuan’s lab is working on a project to investigate the pathogenic role of mesenchymal stem cells (MSC) and endothelial progenitor cells (EPCs) in the development and progression of chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (PAH) using isolated cells and specimens from CTEPH patients who underwent pulmonary endarterectomy and idiopathic PAH patients who underwent lung or lung/heart transplantation.

Ex Vivo Lung Program and Stem Cell Banking

"Figure 1: Strategies for development of 3D scaffolds of acellular human and porcine lungs for high throughput analysis" Courtesy Biomaterials, 35 (2014) 2664-2679 via ScienceDirect ( Zain Khalpey leads a productive clinical and translational cardiothoracic research program, Ex Vivo Lung Program, and an active stem cell banking program, Cardiopulmonary Stem Cell Bank. The Ex Vivo Lung Program offers a method of improving the quality of lungs removed from donor cadavers, making more lungs suitable for transplantation. His research on translational tissue regeneration evolved from past doctoral basic science studies in metabolomics (the metabolites in a biological cell, tissue, organ or organism, which are the end products of cellular processes) and cell survival. His laboratory at the UA focuses on basic and translational research involving organogenesis (the formation and development of organs), organ preservation and tissue regeneration. He also is pioneering the use of a 3-D bioprinter to aid in his organogenesis and tissue regeneration goals. His team currently is working on a 3-D bioprinter that can print using “bioink” containing a patient’s own stem cells. Dr. Khalpey is engaged in ex vivo reconditioning of marginal human hearts and lungs, which will generate functional lung and heart tissue that ultimately can be used for transplantation. This reconditioning process uses human cadaveric lungs that are decellularized (chemically stripped of their cells, leaving behind the extracellular tissue) to create a functional lung bioscaffold. This structure then can be “re-seeded” with autologous (a patient’s own) stem cells to rebuild the organ. With limited hearts available for transplantation, Dr. Khalpey is initiating “bridge-to-regeneration” trials in which autologous stem cells are injected into a patient’s failing heart to offer hope for increased regeneration and recovery.