Regenerative medicine and adult stem cell biology

The fields of regenerative and anti-aging medicine are forever changing the way we view aging and our health. Today, it is no longer about the traditional practice of medicine in which we treat patients symptoms, rather the renaissance lies with the scientific discoveries that damaged, degenerative and diseased tissues can be repaired and even replaced using stem cell based medicines.

Adult stem cells (ASCs)

ASCs are at the center of this field of regenerative medicine. ASCs are rare cells in our bodies that not only have the unique capacity for self-renewal to remain a stem cell, but also develop into mature cells that make up all tissues and organs of the body. ASCs are located in all tissues and organs where they can assist in tissue repair. They are responsible for all aspects of tissue regeneration including, for example healing cuts on our skin, tears in our muscles and tendons and for replacing the lining cells of our intestinal tracks that are lost constantly through daily food intake and metabolism. With increasing age, the number and functions of these critically important stem cells decreases. As a result, our tissue repair mechanisms slow down and as older adults we do not repair ourselves as efficiently as we do when we are children and young adults. We and others are working to identify human stem cells that can be clinically used in tissue repair and regeneration.   In addition to our studies on human mesenchymal stem cells, we are using our “humanized” mice to investigate the role of these different populations of ASCs for in vivo tissue regeneration.

Learn more at the Harvard Stem Cell Insitiute Center - Humanized Neonatal Mouse Center

Human Mesenchymal Progenitor Stem Cells

Mesenchymal stem cells (MSCs) represent a promising cell-based therapy option for enhancing endogenous tissue repair and for suppressing autoimmunity due to their ease of isolation from bone marrow (BM), their expansion capability in vitro, and their differentiation potential and immunomodulatory properties.  However, the  method of isolation of BM mesenchymal stem/stromal cells (MSCs) is a limiting factor in their study and therapeutic use.  MSCs are typically expanded from BM cells selected on the basis of their adherence to plastic, which results in a heterogenous population of cells.  Prospective identification of the antigenic profile of the MSC population(s) in BM that gives rise to cells with MSC activity in vitro would allow the preparation of very pure populations of MSCs for research or clinical use.  To address this issue, we used polychromatic flow cytometry and counterflow centrifugal elutriation (CCE) to identify a phenotypically distinct population of mesenchymal stem/progenitor cells (MSPC) within human BM.  The MSPC activity resided within a population of rare cells based on their small size that were CD45-CD73+CD90+CD105+ cells and lacked CD44, the common MSC marker.  In culture, these MSPC adhere to plastic, rapidly proliferate, and acquire CD44 expression.  They form CFU-F and are able to differentiate into osteoblasts, chondrocytes and adipocytes under defined in vitro conditions.  Their acquired expression of CD44 can be partially downregulated by treatment with recombinant human G-CSF, a response not found in MSCs derived using conventional methods.  These observations indicate that MSPCs within human BM are rare, small CD45-CD73+CD90+CD105+ cells that lack expression of CD44.

Hall SR, Jiang Y, Leary E, Yavanian G, Eminli S, O'Neill DW, Marasco WA.  Identification and Isolation of Small CD44-Negative Mesenchymal Stem/Progenitor Cells From Human Bone Marrow Using Elutriation and Polychromatic Flow Cytometry. Stem Cells Transl Med. 2013 Aug;2(8):567-78. doi:10.5966/sctm.2012-0155. Epub 2013 Jul 11. PMID:2384700

SDF-1/CXCR4 Axis

The SDF1/CXCR4 axis is critically important for in vivo mobilization of CD34+CXCR4+ stem cells out of their bone marrow “niche” where they can then assist in the periphery in stem cell based regeneration and repair. We have developed human anti-CXCR4 Mabs that are being evaluated in our humanized mouse models as in vivo adjuvant agents that can assist in tissue regeneration.

Xu C, Sui J, Tao H, Aird D, Zhu QK and Marasco WA. Human Anti-CXCR4 Antibodies Undergo VH Replacement, Exhibit Functional V-Region Sulfation and Define CXCR4 Antigenic Heterogeneity. J. Immunol 2007 Aug 15;179(4):2408-18. PMID: 17675502

 

Learn more about our Center for Human Antibody Therapeutics (CHAT) at the Harvard Stem Cell Institute (HSCI)