Bone marrow (BM) is a rich source of adult stem cells including blood forming stem cells currently used in over 55,000 bone marrow transplants each year . Other bone marrow stem and progenitor cells have recently been found to be increasingly useful for a widening array of regenerative therapies. The objectives of this research is to further develop 3 novel enabling tools to address the unmet needs for a minimally invasive harvest of bone marrow, the rapid processing of marrow, and the targeted delivery of BM derived stem cells.
BM transplantation has been used to treat patients with a wide variety of disorders. Preclinical studies and a rapid progression of clinical studies suggest that marrow-derived stem cells may be utilized to mediate repair and regeneration of a variety of damaged tissues including in orthopedics, for treatment of damaged cardiovascular systems, neural tissues, and for organ systems such as liver, kidney & pancreas.
The effectiveness of any marrow stem cell therapy depends particularly on the numbers and function of harvested stem cells, as numbers generally correlate positively with clinical outcome. In addition the ease of obtaining marrow, reproducibility and quality of the marrow are critical for enabling use in the clinic and optimizing health benefits.
HARVEST: Current procedures for harvesting BM are invasive, slow, painful and inefficient, and utilize a large bone marrow aspiration needle, which must repeatedly puncture the hip bone to serially harvest small BM volumes. This can require up to 200 separate puncture/aspirates, often under general anesthesia. Aspiration of >5ml per puncture results in marrow highly diluted with peripheral blood. We have developed a novel powered harvesting device, to address the need for an effective minimally invasive approach, under local anesthesia, via a single puncture. Animal studies found a 10X increase in stem cell yield/ml with the device compared to standard harvest needles, and initial clinical trials with the novel system demonstrated safety and efficacy. We propose to develop a 2nd Generation production level harvest system which can be utilized for bone marrow transplantation and to enable many current and future regenerative medicine trials and therapies.
PROCESSING of harvested BM ito enrich for stem cells is critical for cell therapy but labor and time intensive. A new sound based cell separation technology shows promise as a rapid approach to isolate cells from blood. We will further develop this technology for use with marrow.
DELIVERY: Effective stem cell therapy requires targeted cell delivery. Tools to deliver cells effectively to the pancreas do not exist. We have developed a novel catheter designed to optimize for cell delivery to the pancreas, & propose to advance this technology to the clinic.
Statement of Benefit to California:
Bone marrow is a rich source of adult stem cells and have been utilized for over 40 years in the field of bone marrow transplantation. The use of adult stem cells, derived from the patient, or a healthy donor's bone marrow are becoming increasingly important and useful in the field of regenerative medicine.
With more effective tools to enable stem cell therapy, clinicians benefit, with better, more efficient tools which make their clinical work easier and more effective . Patients benefit by having easier marrow harvests, and with better cell content, and potentially better clinical outcomes, and the Payor's benefit (i.e. California's Medi-Cal system), by providing better therapies, more efficiently at less cost with clinical outcomes that should lower overall healthcare costs.
California boasts several of the world's top bone marrow stem cell transplant centers (including Stanford, UCSF, City of Hope, and others). Better bone marrow harvest technologies which ease the donation process in terms of time, inconvenience, pain and potential risks, for healthy donors (allogeneic), and for the patients themselves (autologous transplants), but should also save the hospital and insurance programs money, by taking harvests out of the operating room, and into a rapid , minimally invasive outpatient procedure.
In terms of the growing field of regenerative medicine, many new approaches to treating disease utilizing marrow derived cells are showing promise, including for the treatment of heart attacks, congestive heart failure, peripheral vascular disease, and more recently for neurologic disease and injury (ie Parkinson's) and spinal cord injury. In order to enable bone marrow derived stem cell therapies, tools for the clinician (such as proposed in this CIRM application) are critical to make the process of obtaining the marrow cells (harvest), and subsequent cell processing (to isolate stem cell component) and organ specific delivery.